bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of adrenalectomy and DOCA on the DPN‐ and TPN‐diaphorase activities in the early stages of liver carcinogenesis induced by 3′‐methyl‐4‐dimethylaminoazobenzene
Authors: Hadjiolov D. C.
Published: February 2007

Comparative cytochemical studies on the activity of DPN‐diaphorase, TPN‐diaphorase and some coenzyme‐dependent dehydrogenases revealed marked differences in the degree of liver parenchymal damage of intact and adrenalectomized rats fed 3′‐methyl‐4‐dimethylaminoazobenzene.

The quantity of formazan deposits, that is, the activity of DPN‐and TPN‐diaphorase in intact animals, sharply decreased after rats were fed a carcinogenic diet for 60 days. Coarse formazan granules, in nest‐like formations, occurred in the cells. Enzyme activity did not decrease in adrenalectomized rats treated with 10 mg DOCA weekly. Adrenalectomy and DOCA treatment were nevertheless incapable of providing absolute protection of the liver parenchyma. Coarse formazan granules were detected in the central areas of the liver lobules.

These marked quantitative differences in the degree of liver damage in intact and adrenalectomized rats may indirectly affect the occurrence of “oval cell proliferation” and thus the further progression of malignancy.
Studies on the aetiology of bilharzial carcinoma of the urinary bladder VI. Beta‐glucuronidases in urine
Authors: Abdel‐Tawab G. A. , El‐Zoghby S. M. , Abdel‐Samie Y. M. , Zaki A. , Saad A. A.
Published: February 2007

The pH specificity of β‐glucuronidase enzymes in the urine of cancerous and noncancerous bilharzial patients was investigated.

Bilharzial patients with urine pH above 6.0 and bilharzial bladder cancer patients had heterogeneous urinary β‐glucuronidase activities with distinct pH optima of 5.0 and 7.0, whereas other bilharzial patients and controls showed only the former peak. We suggest that the urinary β‐glucuronidase with a pH optimum of 7.0 is of bacterial origin. This enzyme may also influence the liberation of bladder carcinogens from their excreted glucuronide conjugates.
Rous tumors in monkeys
Authors: Zilber L. A. , Lapin B. A. , Adgighytov F. I. , Shevljaghyn V. Ja. , Jakovleva L. A.
Published: February 2007

Macaca rhesus, Macaca irus, Macaca nemestrina, Papio hamadryas and Cercopithecus aethiops monkeys are susceptible to Rous sarcoma virus (RSV) (Carr and Schmidt‐Ruppin strains). After intramuscular or subcutaneous injection of RSV‐infected chicken cell suspensions or cell‐free extracts of the chicken Rous sarcoma virus, they develop tumors at the sites of inoculation.

These tumors appear after different periods of time, ranging from 15 up to 35 days after inoculation of the virus‐containing material. After an initial period of continuous growth (sometimes as long as 7 months), the tumors regress in most cases.

Histologically, the tumors are polymorphous fibrosarcomas which do not produce metastases.

The oncogenicity in monkeys of the Carr or Schmidt‐Ruppin strains was of no substantial difference. Only newborn or very juvenile monkeys are susceptible to Rous virus.

The virus may only in some cases be isolated from the simian tumors by inoculation of tumor cell suspensions into chickens.

Monkeys inoculated with Rous sarcoma virus develop virus‐neutralizing antibodies, in most cases very late.
Demonstration of common specific antigen(s) in mouse and hamster polyoma tumors
Authors: Hellström I. , Sjögren H. O.
Published: February 2007

A specific, non‐virion antigen common to mouse and hamster polyoma tumor cells was detected by the colony inhibition (CI) technique. This antigen was not readily detectable by transplantation methods.
Tumour initiation by natural and contaminating asbestos oils
Authors: Roe F. J. C. , Walters M. A. , Harington J. S.
Published: February 2007

Oils are present “naturally” in crocidolite and amosite asbestos. During processing, transport and storage, asbestos tends to be contaminated with other oils, including jute oil.

Large commercial samples of crocidolite and amosite were extracted, by means of specially purified solvents, to remove both primary and contaminating oils.

The later were tested for tumour‐initiating activity by twice‐weekly application to the dorsal skin of mice alternating with once‐weekly application of the tumour‐promoting agent, croton oil.

Significantly more papillomas and, in the case of amosite oil, carcinomas, arose in response to treatment with asbestos oil plus croton oil than in response to croton oil only.

The tumour‐initiating response was weak but reasons are given for not rejecting the possibility that the oils play a significant role in the induction of cancer by asbestos.
Counting and sizing of tumor metastases in experimental oncology
Authors: Boeryd B. , Ganelius T. , Lundin P. , Mellgren J.
Published: February 2007

Practical presumptions and mathematical problems in estimating the number and size of tumor metastases in experimental oncology are discussed.

The estimations should be based upon microscopic investigation. However, considerable biologic variation necessitates the use of large numbers of experimental animals, which makes the serial sectioning of the organs—applied to other biological materials and thoroughly discussed by earlier workers—impossible in practice.

Therefore, formulae are presented for the calculation of the actual number and total volume of the metastatic corpuscles per unit volume of an organ, from the number and total area of their images in a limited number of sections taken at arbitrary levels through the organ. The influence on the calculations of variations in size and shape of the corpuscles is studied.

The formula for volume was found to hold generally. The estimation for number, which was found to be influenced by the size and the shape of the corpuscles, is further tested on an experimental material of metastases in liver and lungs from a mouse sarcoma. It is concluded that, with the techniques used, the error of the mathematical estimation of the number of metastases is less than 16%. By double determinations it is shown that the statistical error for individual determinations is considerably larger than the maximum error incurred by mathematical estimations.
Transplantation behavior and cytogenetic characteristics of a spontaneous reticulum cell sarcoma in the golden hamster
Authors: Haemmerli Gisela , Zweidler Alfred , Sträuli Peter
Published: February 2007

During a period of 2 1/2 years, 33 spontaneous reticulum‐cell sarcomas arose in our colony of golden hamsters. One of the tumors, made transplantable in the solid and the ascitic form, is described with regard to behavior in homologous hosts and to cytogenetic characteristics. During four years of transplantation, the tumor changed its pattern of growth and, after an initial phase of localized growth, displayed a leukemialike mode of spread resulting in the death of the hosts on the 6th or 7th day irrespective of site of transplantation. Animals of the same passage reacted differently to tumor implantation: some hamsters developed large tumors without tumor cell spread, others showed very small tumors with heavy tumor cell dissemination. These different modes of growth are assumed to be dependent on host factors.

Chromosome analyses were carried out on tumor cells of different transplantation generations. The chromosomes in cells of the 38th generation did not differ from normal hamster cells, except for a higher variation in the number of chromosomes. Within the next 15 passages the karyotype changed considerably, but from then on remained stable with a stemline of 44 chromosomes and six markers. The late replication pattern of sex chromosomes and of most of the autosomes seems to be the same for both normal hamster cells and tumor cells.

The DNA content of the tumor cells was found to correspond to the modal chromosome number.

No causal relationship between changes in growth characteristics and in karyotype could be established.
Chemotherapeutic activity and pathological effects of an alkylating agent of short half‐life designed for intra‐arterial infusion (CB 1850)
Authors: Cobb L. M.
Published: February 2007

A short half‐life alkylating agent designed for intra‐arterial infusion, p‐[2,3‐di(2‐bromoethylthio)‐n‐propyloxy]benzoic acid (CB 1850), was tested against the Walker tumour growing in the hind limb of rats. When administered intravenously CB 1850 was without effect at a dose which produced 100% cure when injected into the artery supplying the tumour. Although the drug produced a response in the benzo (a) pyrene‐induced fibrosarcoma, there were no cures. There was evidence of a biological half‐life for the drug of the same order as the in vitro value of 4.8 seconds.
Vitamin B12 levels in whole blood, plasma, and blood cells in transplantable rat leukaemias
Authors: Bonelli M. , Rinaldini L. M.
Published: February 2007

Vitamin B12 levels in whole blood, plasma, and red and white cells were determined by microbiological assay in normal and leukaemic A × C inbred rats. The concentration of B12 in white cells was 200 to 300 times higher than in red cells in both groups.

A marked increase in the B12 content of whole blood was observed in the leukaemic animals which was of the same order of magnitude as the increase in the number of white cells.

The concentration of B12 in red cells was the same in normal and leukaemic blood. That in plasma and white cells was only slightly increased in leukaemia. Therefore, the overall increase in blood B12 is attributable to the increase in the number of white cells in the leukaemic animals.
Further studies on the membrane immunofluorescence reaction of Burkitt lymphoma cells
Authors: Klein Eva , Clifford Peter , Klein George , Hamberger Carl‐Axel
Published: February 2007

The specificity of the membrane immunofluorescence reaction obtained upon the exposure of viable Burkitt lymphoma biopsy cells to the sera of certain Burkitt lymphoma patients (Klein et al., 1966 a, b) was studied by testing representative negative and positive sera against Burkitt lymphoma cells and normal bone marrow cells from the same donor, as well as against a panel of allogeneic normal lymph node cells and chronic myeloid leukemia cells from Swedish patients. Sera giving highly positive reactions with Burkitt lymphoma cells failed to react or reacted only exceptionally with normal bone marrow cells of the same donors or the allogeneic non‐Burkitt target cells. In contrast, an isoimmune serum from a multiply transfused donor gave highly positive reactions against both Burkitt and non‐Burkitt target cells. Taken together with previous results, these findings speak against the involvement of blood group or transplantation antigens, leaving two main explanations: (a) a tumor‐specific reaction, similar to the findings on virus‐induced mouse lymphomas: (b) preferential non‐specific binding to Burkitt lymphoma cell surfaces of some globulin fraction appearing in the serum of Burkitt lymphoma patients after chemotherapeutically induced regression.
Coulter counter analysis of lymphoma differentiation patterns in AKR mice with lymphoid leukaemia
Authors: Metcalf D. , Brumby M.
Published: February 2007

Using a Coulter counter, we obtained cell size distribution patterns from thymic and lymph‐node lymphoma tissues in AKR mice. Distribution patterns were different in all animals examined but, within individual mice, the lymphoma deposits in various locations showed identical patterns. Lymphoma cell patterns were maintained on first passage transplantation to normal AKR mice. No correlation was observed between lymphoma cell distribution patterns and lymphoma alkaline phosphatase contents or the rates of division of the lymphoma cells as determined by tritiated thymidine uptake studies.
The effect of Rous sarcoma virus (Schmidt‐Ruppin strain) on the chromosomes of human leucocytes in vitro
Authors: Schendler Shirley , Harris R. J. C.
Published: February 2007

Human leucocyte cultures have been incubated in vitro with Rous sarcoma virus of the Schmidt‐Ruppin strain (RSV(S‐R)). Mitosis appeared to be inhibited to a degree dependent on the virus concentration. However, and contrary to other reports, the incidence of chromosome breaks (6 in 612 metaphases examined) in such cultures did not significantly differ from that found in controls (3 in 729) and was less than that for cultures incubated with a microsome fraction from chick embryo tissue homogenate (10 in 262).

5‐Bromodeoxyuridine (BUDR) produced 17 breaks in the 77 metaphases examined (22%) and the Negroni mycoplasma (from leukaemic bone‐marrow) gave 21 breaks in the 70 cells analysed.
Transformation in vitro de cellules de hamster chinois par l'adénovirus 12: Étude cytogénétique
Authors: Brailovsky Carlos , Wicker Rene , Rolando Cassingena Horacio Suarez Et
Published: February 2007

Chinese hamster cells can be transformed in vitro by adenovirus 12. These cells synthetise specific neo‐antigen (s), are tumorigenic for this animal species and show chromosomal alterations which are independent of malignant conversion.
Two spontaneously transformed cell lines derived from the same hamster embryo culture
Authors: Diamond Leila
Published: February 2007

From a single primary culture of pooled hamster embryos, two morphologically distinct, malignant cell lines have evolved in the absence of experimentally applied selective factors, chemical, physical or viral. The cells of both sublines are male. One subline, designated Nil‐1, is extremely pleomorphic with lobulated nuclei and micronuclei. It was tumorigenic at the 35th passage (18 weeks) after initiation of the primary culture. The second subline, designated Nil‐2, is fibroblastic and required 30–45 more subcultures than Nil‐1 to become tumorigenic. The malignant properties of Nil‐1 and Nil‐2 were not correlated with any specific chromosome changes. At a time when Nil‐2 cells were still sensitive to contact inhibition and were not tumorigenic, they could be transformed by polyoma virus but not by SV40. The parent primary culture, however, was susceptible to transformation by SV40.

Neither subline contained SV5 or lymphocytic choriomeningitis viral antigen or specific complement fixing antigen induced by polyoma virus, SV40, Rous sarcoma virus or adenovirus types 7, 12, 18, 21, or 31. No cytopathogenic agent and no mycoplasma could be isolated from the parent culture or sublires; no new transplantation antigen could be demonstrated. The possibilities in the etiology of the transformation are discussed.
Biological and chemotherapeutic studies on primary mammary tumors in C3H and C3HO mice
Authors: Gelzer J. , Loustalot P.
Published: February 2007

A reproducible chemotherapy assay system using primary mammary tumors in C3H and C3HO mice is described. These tumors, although possibly hormone‐dependent to a minor extent, are not steroid‐sensitive and their response to accepted anti‐cancer compounds follows in general that of classical transplantable rodent tumors.
Clinical evaluation of a new alkylating agent, Azetepa, in one hundred and twenty‐five cases of malignant tumors
Authors: Choy Daniel S. J. , Arandia Jose , Rosenbaum Isaac
Published: February 2007

A new alkylating agent, Azetepa, is described. Our clinical experience in 125 patients with a variety of solid tumors is presented. Azetepa is useful chiefly in the treatment of lymphomas, mammary carcinoma, and carcinomas of the female genital tract. Its effectiveness in carcinomas of the digestive tract and accessory organs is comparable to that of the fluorinated pyrimidines. It can be administered via all conventional routes. Toxicity was very low; no deaths due to hematologic causes occurred. There was no hepato‐renal toxicity. Tentative recommendations are made for dosages and routes of administration.
An experimental model for studying factors which influence metastasis of malignant tumors
Authors: Karrer K. , Humphreys S. R. , Goldin A.
Published: February 2007

Implantation of Lewis lung tumor into the leg muscle of BDF1 male mice resulted in tumor growth at the site of implantation. Metastasis to the lungs regularly occurred, early in the course of the disease, when the primary tumor was small and the mouse was capable of tolerating both surgery and chemotherapy.

Treatment with cyclophosphamide alone was relatively ineffective in increasing the survival time of the animals and failed to increase the percentage of survivors.

Radical surgery, performed early in the course of the disease, resulted in “cures” of almost 60% of the animals. Later, after definite metastasis had occurred, surgery alone was ineffective.

Surgery plus adjuvant chemotherapy was in some instances more effective than surgery alone or chemotherapy alone in yielding “cures”. Also, in many instances, the combination constituted more effective treatment in increasing the survival time of the animals. However, cumulative drug toxicity appeared to interfere with the potential of the combination modality of therapy.
Distribution of deoxyribonuclease activities in the subcellular fractions of mammary tumors of C3H mice
Authors: Georgatsos J. G. , Polyzonis M. , Palavradji D. , Symeonidis A. , Albanides D.
Published: February 2007

The distribution of acid and alkaline deoxyribonuclease activities in the subcellular fractions of mouse mammary tumors of C3H mice has been studied. All sedimentable particles exhibit both activities. However, per mg of protein, the mitochondrial fraction is more active with respect to the acid deoxyribonuclease, while the alkaline deoxyribonuclease (exonuclease) shows highest specific activity in microsomes. Further fractionation of microsomes on sucrose gradients showed that exonuclease activity is present in deoxycholate‐soluble structures and not in ribosomes.
Effet des rayons x sur la leucémogénèse dbs souris akr: Role dǒune lésion généralisée du système hémopoïétique
Authors: Jullien Pierre , Rudali Georges
Published: February 2007

AKR mice were irradiated 1, 8, 15 and 22 days after birth (175 R total irradiation). In these animals, lymphoid leukemias appeared at the age of 5 months, as opposed to 8 months in unirradiated mice. Injection ofisologous bone marrow after the last irradiation had no influence on the accelerated appearance of the leukemias. Irradiation of the anterior half of the body only was also capable of accelerating the appearance of lymphoid leukemias.

In contradiction, in C3H mice, the injection ofisologous bone marrow after a series of irradiations did prevent the appearance of leukemia, and partial body irradiation was not leukemogenic. Injection of either C3H or AKR bone marrow to F1 hybrid mice (AKR × C3H), irradiated under the same conditions as AKR mice, diminished the appearance of leukemias to a limited extent at the age of 5 months. Those F1 hybrids which, after irradiation and subsequent injection of AKR bone marrow, did not become leukemic at the age of 5 months, developed leukemia originating from the AKR cells at a later age. Some newborn (AKR × C3H) F1 hybrids were injected with AKR bone marrow after the irradiation (175 R); the three following irradiations were carried out after the bone marrow preparation had been administered. In these animals, leukemia, originating from the injected AKR cells, appeared at the age of 5 months.
Uptake of sodium fluorene‐2‐selenonate‐75Se by spleen and of sodium n‐7‐fluorenylacetamido‐2‐selenonate‐75Se by tumor in mice
Authors: Agrawal Krishna C. , Ray F. E.
Published: February 2007

Two new radioactive compounds, sodium fluorene‐2‐selenonate‐75Se, (II), and sodium N‐7‐fluorenylacetamido‐2‐selenonate‐75Se, (V), have been synthesized. The tissue distribution of these compounds in tumor‐bearing mice has been studied at different time intervals. The first compound localized itself in spleen, and its distribution was also studied in tumor‐free mice. This compound gave quite favorable ratios of concentration in spleen to the concentration in tissues. The use of this compound in splenic scanning is suggested. The second compound was concentrated in tumor to a greater extent than in the vital organs, from which it was eliminated later, showing the affinity of the compound for the tumor tissue.
Summarizing indices for comparison of cancer incidence data
Authors: Doll Richard , Cook Paula
Published: February 2007

The desirability of achieving agreement on a method of summarizing cancer incidence is emphasized, and the advantages and disadvantages of the use of the traditional standardized incidence rates are discussed.

It is concluded that:

No single index is capable of replacing the individual sex‐ and age‐specific incidence rates, and these should always be presented when basic cancer incidence data are published.

For aetiological studies age‐specific incidence rates can usefully be summarized in two indices, one (a truncated standardized incidence) showing a standardized incidence over a restricted age range, and the other indicating the rate at which cancer incidence increases with age.

An appropriate truncated rate for most epithelial cancers is one for the age range of 35 to 64 years, using weights of 6, 6, 6, 5, 4 and 4 for the individual 5‐year age groups, derived from Segi's (1960) world standard population. For other cancers, age ranges of 0 to 14 years and of 0 to 44 years would be more suitable, with weights of 12, 10 and 9, and 12, 10, 9, 9, 8, 8, 6, 6 and 6 for the corresponding 5‐year age groups.

An indication of the general character of a given set of incidence data may be obtained by calculating the ratio of the rates at ages 55 to 64 years and at 35 to 44 years for a combined group of cancers that normally increase rapidly in incidence with age.

Further research on practicable ways of indicating the shape of the age‐incidence curve for individual types of cancer is required.
Relationship between DNA synthesis and cell density in normal and virus‐transformed cells
Authors: Macieira‐Coelho A.
Published: February 2007

Three normal human and two normal bovine fibroblastic lines were compared with one of the human lines transformed with Rous sarcoma virus (RSV), one human line transformed by Simian virus (SV 40) and the two bovine lines transformed with RSV, with respect to DNA synthesis between subcultivation and cell crowding. It was found that the rate of DNA synthesis during a 24‐hour period was higher in the transformed cells at the terminal cell density of the respective normal lines. The results gave further support to the previous suggestion that “unrestrained growth transformation” can be expressed by comparing DNA synthesis with cell density. In one of the transformed cultures DNA synthesis stopped at a cell density twice that of the controls. In the three other transformed cultures DNA synthesis never stopped. This difference in behaviour can be explained by a loss of cell cycle inhibition combined with different affinities of the cells towards their substrate.
Mitotic cycle and cell differentiation in squamous cell carcinomas
Authors: Frankfurt O. S.
Published: February 2007

The mitotic cycle and cell differentiation in the second generation of transplanted squamous cell carcinomas were studied autoradiographically with the aid of thymidine‐3H. The results obtained were compared with those reported earlier on normal squamous epithelium of the mouse forestomach, from which these carcinomas originated.

Proliferation in squamous cell carcinomas was significantly accelerated, mainly as a result of shortening of the G1 phase. The rate of cell differentiation changes less significantly when measured by the duration of the maturation phase or of cell lifetimes in the differentiated state. The percentage of cells which were destined to differentiate was 17–34% out of all cells in the mitotic cycle in tumors. This value, which in a normal steady state is 50%, characterizes the extent of disturbance of balance between cell proliferation and differentiation.

The most significant difference in the cell cycle for normal and tumor cells is observed in the phase at which cells that will differentiate get out of the mitotic cycle; this is the presynthetic phase for normal cells and premitotic phase for cancer cells. The significance of this qualitative difference in the life cycles of normal and cancer cells is discussed with respect to disturbance of steady state and progressive growth.
Structural and metabolic distinction between Morris Hepatoma 5123 A and normal rat liver
Authors: Fiala Silvio , Fiala Anna E.
Published: February 2007

Evidence is presented to show that Morris Hepatoma 5123 A differs strikingly from homologous normal tissue in its metabolic and structural aspects.

The succinoxidase activity of Hepatoma 5123 A is only 40% that of liver, while anaerobic glycolysis, although relatively low, is nevertheless some 100% higher than in normal liver. The mitochondrial content of Hepatoma 5123 A is about 40% that of the normal liver cell. The amount of material in the microsomal fraction is reduced in the hepatoma and there is a pronounced shift in the distribution of RNA in favor of the RNA in the nuclear and supernatant fractions. Hepatoma 5123 A shares all of these characteristics with other known tumors.

In distinction to rapidly growing tumor and proliferating tissue, Hepatoma 5123 A has about the same or higher dCMP‐ase activity as normal liver, while dCMP‐deaminase is about 20 times as high as in normal rat liver.

In addition to the quantitative depletion of mitochondria, Hepatoma 5123 A shows also a depletion in the flavin and cytochrome c content of the mitochondrial soluble matrix. In contrast to normal mitochondria, in which the administration of 3,3',5‐tri‐iodothyronine led to a an increase several times the normal value, in the activity of α‐glycerophosphate dehydrogenase, the level of this enzyme in tumor mitochondria remained unchanged following the administration of triiodothyronine.

In contrast to normal liver, Hepatoma 5123 A has shown in all subcellular fractions the presence of polarographically active, non‐protein SH‐compounds. In normal rat liver these compounds appear only in the mitochondrial fraction and their level is much lower than in Hepatoma 5123 A.

It is suggested that the Warburg type of metabolism in Hepatoma 5123 A may be a manifestation of structural and functional insufficiency of preformed cytoplasmic elements.
Tumour‐specific antigenicity of aminoazo‐dye‐induced rat hepatomas
Authors: Baldwin R. W. , Barker C. R.
Published: February 2007

Tumour‐specific transplantation antigens have been demonstrated in rat hepatomas induced with 4‐dimethylaminoazobenzene (DAB). Resistance to these tumours was induced in syngeneic hosts either by destruction of developing tumour grafts or by implantation of heavily irradiated tumour. These rat hepatomas were shown to possess individual antigenicities so that induction of immunity against one hepatoma did not confer on the treated rat any resistance to a second hepatoma also induced by DAB.

Resistance could be passively transferred to normal rats with peritoneal exudate cells from immune donors. These peritoneal exudate cells, containing approximately equal proportions of macrophages and lymphocytes, carried the same specificity as the immunizing tumour in that they were without influence on the growth of other DAB‐induced hepatomas.
Erythropoietic stimulating factor (ESF) effects on induced and spontaneous murine leukemia
Authors: Leaders Floyd E. , Chapman A. L. , Kornhaus Barbara , Nielsen Anne H. , Werder Alvar A.
Published: February 2007

Erythropoietin (ESF) has been found to increase the incidence of leukemia and mammary tumors in female conventional CFWw mice during a 19‐month observation period after administration of a single dose of ESF and leukemia extract. ESF alone also increased the number of leukemias in female conventional mice. These increases apparently were sex‐related. The increase in the incidence of leukemia is postulated to be through a mechanism of “activation” of endogenous virus since a similar enhancement was not recorded in ex‐axenic animals receiving similar treatment. Instead, in the ex‐axenic group ESF produced an apparent decrease in the incidence of leukemia. These observations have been related to the relative number of virus‐like particles in the tissues of the conventional and ex‐axenic CFWw mice.
Tritium uptake, half‐lives and radiation doses in tissues of cancer patients treated with tritiated 2‐methyl‐1: 4‐naphthaquinol diphosphate
Authors: Chipperfield Barbara
Published: February 2007

Comparisons of the uptake into tumour biopsies 30 min after intravenous or intra‐arterial injections showed that tumours of gastrointestinal origin took up significantly greater amounts of the tritiated drugs than did any other group of tumours, and with other types of tumours some individual biopsies showed very high tumour specific activities after intra‐arterial injections. The tritium in the tumour disappeared by two exponential decay processes, one with a half‐life of 1.35 days and the other with a half‐life of 14.4 days. The ratio of the concentration of the long‐lived component to that of the short‐lived component was 0.33.

Tritium estimations on normal tissues taken at autopsy from patients who received only one injection of the tritiated drug showed that the biological half‐life in normal tissues ranged from 5.7 days (heart) to 34.5 days (long‐lived component in brain). The initial specific activity in μc/g for each c/kg injected ranged from 71 (long‐lived component in brain) to 505 (kidney).

After a single injection of 1 c of the drug per kg body weight, the greatest doses of radiation were received by the kidney (1,600 R), testis (1,300 R), liver (1,050 R) and brain (990 R). The lowest doses were received by skeletal muscle (395 R) and bone marrow (604 R).

The radiation dose in the tumour depends on the initial concentration and the half‐life in the tumour. Initial tumour concentrations of 5–8 mc/g wet tissue should give radiation doses in the therapeutic range after a single injection.
Excretion of tritium after therapeutic injections of tritiated 2‐methyl‐1: 4‐naphthaquinol diphosphate in cancer patients
Authors: Chipperfield Barbara
Published: February 2007

This paper describes investigations on the excretion of tritium in the urine, breath and faeces after therapeutic injections of tritiated tetra‐sodium 2‐methyl‐1 :4‐naphthaquinol diphosphate in patients suffering from advanced malignant disease. Most of the tritiated material is excreted in the urine, a very small percentage appears in the breath as tritiated water, and an even smaller percentage appears in the faeces in the first three days after an injection.

The percentage in the urine seemed to be related to the weight of compound injected in small doses, but larger doses were followed by the excretion of a disproportionately high percentage of the injected tritium. A few people also excreted an extremely high percentage in the urine even after comparatively small doses. This may be a result of alterations in liver metabolism.

Examination of the urinary excretion products by chromatography showed that, during the first 24 hours, most of the tritium was in a glucuronic acid conjugate of menadiol. There were also varying quantities of other substances, including menadiol sulphate, menadione or 1 :4‐naphthaquinone, menadiol disphosphate and an unknown compound which appeared to be another conjugate of menadione or 1 :4‐naphthaquinone. After the first 24 hours the urinary excretion products were only menadiol disphosphate and the conjugate of menadione or 1 :4‐naphthaquinone.

The specific activity of water in the breath was greatest in the first 24 hours and was roughly proportional to the dose injected. On average, 3% of the injected tritium was present in the body as tritiated water.

The precautions taken in nursing these patients are discussed.
Comparaison des actions hépatocancérogènes de la diéthylnitrosamine et du p‐diméthylaminoazobenzène
Authors: Lacassagne A. , Buu‐Hoï N. P. , Giao N. B. , Et R. Ferrando L. Hurst
Published: February 2007

Earlier experiments carried out with the liver carcinogen p‐dimethylaminoazobenzene (DAB) have been repeated with another liver carcinogen, diethylnitrosamine (DEN). Nine different experiments were performed, using 84 male Wistar rats. The results were the reverse of those obtained with DAB. With the latter, a protein‐poor diet or a simultaneous administration of reserpine accelerates the process of cancerization, while addition to the carcinogen of certain phenolic ketones or of o,p'‐dichlorodiphenyl‐dichloroethane (o,p'‐DDD) inhibits it. With DEN, neither variations in the diet nor reserpine have any marked effect on the cancerization process, while the phenolic ketones and o,p'‐DDD accelerate it.

DAB is far more toxic to the hepatocytes, whereas DEN is more toxic to the cells of the connective‐vascular system of the liver.

As is the case with DAB, the carcinomas produced by DEN have their origin in biliary stem‐cells, the different histological types of the tumours merely representing varying degrees of cellular differentiation.
Étude ultrastructurale d'un virus murin sarcomatogéne (MSV)
Authors: Leclerc J. C. , Silvestre D. , Lévy J. P. , Oppenheim S. , Varet B.
Published: February 2007

The structure of tumours induced in mice and rats by the mouse sarcoma virus was studied with the electron microscope. Cultures of whole mouse embryo cells infected in vitro by this virus and subsequently transformed, as well as non‐transformed cultures, were also examined. All the tumours and cultures were carrying a large amount of viral particles whose distribution and structure inside the cells were investigated.
Induction of cancer of the glandular stomach in rats by 20‐methylcholanthrene
Authors: Arkhipov G. N.
Published: February 2007

The effect of 20‐methylcholanthrene (Experiment No. I) and the combined action of ephedrine hydrochloride and 20‐methylcholanthrene (Experiment No. 2) on the mucosa of the glandular stomach was studied in 25 rats. The application of the two chemicals was carried out by means of specially constructed containers which were inserted into the wall of the glandular stomach. Polyethylene‐encased wicks led from the container, touching the gastric mucosa with their tips. The chemicals were slowly pumped by stomach action through the wicks on to the mucosa. The experiments lasted from 14 to 20 months. In Experiment No. 1 (32 rats) stomach tumours developed in 5 rats, in Experiment No. 2 (21 rats), in 7 rats. Most of the tumours were adenocarcinomas. The tumours were large and invaded the serosa of the stomach. In Experiment No. 2 five tumours out of seven showed metastasis in various organs and tissues of the abdomen.
The carcinogenic activities in mice of compounds related to benz[a]anthracene
Authors: Boyland E. , Sims P.
Published: February 2007

The carcinogenic activities of a number of aromatic hydrocarbons have been compared with some metabolic intermediates by subcutaneous injection into C57 black mice. The monohydroxymethyl derivatives of 7,12‐dimethylbenz[a]anthracene and some related compounds were found to be active carcinogens, but were much less so than the parent hydrocarbon. Epoxides formed at the K‐region ofchrysene, benz[a]anthracene, 7‐methylbenz[a]antnracene and dibenz[a,h]anthracene produced tumours when given at highdose levels, but were not as active as the parent hydrocarbons. The epoxide derived from phenanthrene was inactive.
The carcinogenic activities in mice of compounds related to 3‐methylcholanthrene
Authors: Sims P.
Published: February 2007

A number of derivatives of 3‐methylcholanthrene have been tested for carcinogenic action by injection into C57 black mice. 1‐ and 2‐Hydroxy‐3‐methylcholanthrene and 3‐methylcholanthrene‐1‐ and 2‐one were active carcinogens, but cis‐1,2‐dihydroxy‐3‐methylcholanthrene showed only weak activity. The hydrocarbon, 3‐methylcholanthrylene (1,2‐dehydro‐3‐methylcholanthrene). was an active carcinogen. 11,12‐Epoxy‐11,12‐dihydro‐3‐methylcholanthrene showed weak carcinogenic activity whereas cis‐11,12‐dihydro‐11,12‐dihydroxy‐3‐methylcholanthrene was inactive.
Attempts to produce carcinogenesis in organ cultures of mouse prostate with polycyclic hydrocarbons
Authors: Röller Manuela R. , Heidelberger Charles
Published: February 2007

Pieces of C3H mouse prostate were maintained in organ culture with Eagle's MEM

Abbreviations used: 20‐(3)Methylcholanthrene, MCA; 1,2,3,4,‐dibenzanthracene, 1,2,3,4‐DBA; 1,2,5,6‐dibenzanthracene, 1,2,5,6‐DBA; 9,10‐dimethyl‐1,2‐benzanthracene, DMBA; minimal essential medium, MEM.

medium and 10 % horse serum in the presence and absence ofpolycyclic hydrocarbons, stilbestrol, and testosterone. With 1,2,5,6‐dibenzanthracene, methylcholanthrene, and 9,10‐dimethyl‐1,2‐benzanthracene massive hyperplasia, anaplasia, abnormal mitoses, and invasion of pleomorphic epithelial cells through the basement membrane were observed. Similar observations were made, but to a lesser degree, with stilbestrol. With the controls there was moderate hyperplasia and little anaplasia, while testosterone promoted normal differentiation. With the non‐carcinogenic 1,2,3,4‐dibenzanthracene, considerable hyperplasia but little anaplasia was produced. In all cases the viabilities were good and comparable. Prostate pieces from organ cultures treated with the three carcinogenic hydrocarbons were implanted into 872 C3H mice under a variety of conditions, but no tumors were induced. Nevertheless, this system served as the foundation for the subsequent achievement of carcinogenesis in vitro.
DNA, RNA and hemoglobin cytophotometry of maturing erythroid cells from liver nodules in rauscher virus infected mice
Authors: Sundelin Pär , Adams Lawrence R.
Published: February 2007

Cytophotometrically estimated cellular amounts of DNA, RNA and hemoglobin were compared in erythroid cells from liver nodules of Rauscher virus infected mice and from bone marrow of mice made anemic with phenylhydrazine. Atypical erythroblastoid cells with small amounts of hemoglobin from Rauscher virus infected animals had greater amounts of RNA per cell than cells with similar amounts of hemoglobin from phenylhydrazine treated mice. Heavily hemoglobinized cells from virus treated animals tended to have postmitotic amounts of DNA, less cellular RNA and poorer correlation between cellular amounts of RNA and hemoglobin, than phenylhydrazine stimulated bone marrow cells. The cytochemical data support the concept that some Rauscher leukemia cells may contain small amounts of hemoglobin and have a certain capacity for maturation.
Isolation of echovirus type 11 from two cases of Burkitt's tumour and three cases of other tumours
Authors: Munube Germano M. R. , Bell Thomas M.
Published: February 2007

Echovirus type 11 was isolated from two cases of Burkitt's tumour and three non‐Burkitt tumour case. Clinical and serological findings indicate that the virus was not aetiologically related to the tumours from which it was isolated, but that it represented a concurrent infection in the patients. The importance of these negative findings in strengthening the candidacy of reovirus type 3 as a possible causative agent of Burkitt's tumour is discussed.
The pathological effects of subcutaneous injections of asbestos fibres in mice: Migration of fibres to submesothelial tissues and induction of mesotheliomata
Authors: Roe F. J. C. , Carter R. L. , Walters M. A. , Harington J. S.
Published: February 2007

Groups of 20 female CBA mice were injected subcutaneously in two sites with suspensions of crocidolite, amosite or chrysotile asbestos. Each injection consisted of 10 mg fibre suspended in 0.4 ml saline and each animal received 3 injections into each flank at sites well distant from the thorax. For comparison, two groups were similarly treated with crocidolite and amosite from which natural and contaminant oils had been removed by solvent extraction. The most remarkable feature of the results were, first, the apparently specific transport of asbestos fibres of all three types to the submesothelial tissues of the thorax and abdomen; and secondly, the development of extensive inflammatory and proliferative changes in these regions culminating, in 10 instances, in the formation of mesotheliomata. Six animals developed sarcomas at the injection site but, in most mice, there was little cellular response to asbestos in the subcutaneous tissues in contrast to the vigorous reactions seen in serosal membranes. All three types of asbestos induced both injection‐site tumours and distant mesothelial changes and the removal of oils from amosite and crocidolite did not abolish—though it may have reduced—these manifestations of carcinogenic activity.
Separation of specific antibodies to H‐2 isoantigens
Authors: Motet D. , Bergheden C.
Published: February 2007

Antibodies against various H‐2 antigens were separated by an adsorption‐elation procedure. The findings might have implications for both antibody and antigen purification.
Protein synthesizing activity of human neoplastic and normal thyroid tissue in chick embryo mesonephros organ culture
Authors: McCully Kilmer S.
Published: February 2007

Two specimens of human neoplastic tissue, renal cell carcinoma and adenocarcinoma of lung, and one specimen of normal human thyroid tissue were cultured in the chick embryo mesonephros organ culture system according to Wolff's technique, and the protein synthesizing activity of the cultured tissue was assayed by studying the incorporation of l‐leucine‐14C into protein. During one week of culture all three samples of tissue maintained their morphologic integrity, as judged by histologic study, and their metabolic and synthetic activity, as judged by leucine incorporation. After freezing and thawing in glycerinated buffer, the renal cell carcinoma and adenocarcinoma of lung tissue regained protein synthesizing activity during culture in the chick mesonephros system only when the carcinoma fragments were placed in direct contact with the mesonephros fragments. Interposition of the vitelline membrane between the mesonephros and carcinoma fragments prevented restoration of protein synthesizing activity. The possibility is suggested that high molecular weight polymers of undetermined nature are supplied by mesonephros cells for restoration of protein synthesizing activity of frozen and thawed carcinoma cells.
Influence of microbial environment on development of myeloid leukemia in X‐irradiated rfm mice
Authors: Walburg H. E. , Cosgrove G. E. , Upton A. C.
Published: February 2007

The incidence of radiation‐induced myeloid leukemia, to which conventionally reared RF mice are unusually susceptible, has been observed to vary among colonies of RFM mice maintained in different microbial environments. The incidence in germ‐free RFM males exposed to 300 R of X‐irradiation at 5 to 6 weeks of age was only 1%, whereas that in their conventionally reared counterparts was 13%. In similarly irradiated RFM males subjected to microbial shock by transfer from an environment containing a limited number of bacteria to a conventional microbial environment, the incidence was 20%. The results suggest that the incidence of myeloid leukemia varies inversely in relation to the bacterial “cleanliness” of the environment, possibly as a result of associated variations in granulocytopoiesis.
Possible association between pernicious anaemia and leukaemia: A prospective study of 1,625 patients with a note on the very high incidence of stomach cancer
Authors: Blackburn E. K. , Callender S. T. , Dacie J. V. , Doll R. , Girdwood R. H. , Mollin D. L. , Saracci R. , Stafford J. L. , Thompson R. B. , Varadi S. , Wetherley‐Mein G.
Published: February 2007

Several patients with pernicious anaemia have been reported to have developed leukaemia and the suggestion has been made that the two diseases are aetiologically associated.

Sixteen hundred and twenty‐five patients attending eight pernicious anaemia clinics were, therefore, followed from the time of their first attendance to 1 January, 1964, and the observed numbers of deaths from different causes compared with the numbers that would have been expected if the patients had suffered the mortality rates experienced in the country as a whole.

Analysis of the results showed that the data recorded before 1959 were probably biased by the selective inclusion of patients who had survived. Between 1959 and 1963, the number of deaths was significantly increased for pernicious anaemia (14 against 0.7 expected) and for cancer of the stomach (29 against 7.3 expected). Three deaths were attributed to leukaemia against 0.9 expected. For other causes the observed and the expected mortalities were similar (270 and 294.1).

Six other patients in the series are known to have developed leukaemia—3 dying of the disease before 1959—and it is concluded that patients who are under treatment for pernicious anaemia have a slightly increased risk of dying of leukaemia.

In most of the patients who developed both diseases the leukaemia was of the myeloid type (15 out of a total of 21 reported previously or in this series).
Development of immunocytes and immunoglobulin production in long‐term cultures from normal and malignant human lymph nodes
Authors: Nilsson Kenneth , Pontén Jan , Philipson L.
Published: February 2007

Fifteen human lymph nodes have been grown in vitro. Cells from seven of the nodes eventually developed into apparently permanent lines dominated by cells resembling lymphoblasts.

When the results are combined with a previously published series (Pontén, 1967) no difference is found between the frequency at which the phenomenon occurs in lymph nodes obtained from patients without known malignancy (group L), from nodes draining carcinomas (group C), or from malignant lymphomas (group M). It is concluded that the spontaneous establishment of permanent lymphoid cell lines is a characteristic of human lymphoid tissue in general and that no relationship to malignant lymphoma has been proved. A random fibroblastoid growth, apparently unrelated to the appearance of a secondary lymphoid cell production phase, was observed in eight cases, seven of which belonged to group M or C.

Five of seven lines were tested repeatedly for globulin production by immunoelectrophoresis and immunoprecipitation combined with autoradiography. Four lines produced immunoglobulins of the IgG type; the fifth, obtained from a tuberculous node, synthesized IgA. Each cell line produced only one detectable molecular species, suggesting a monoclonal origin of the immunoglobulins. The light chains were exclusively of the kappa type, whereas the heavy chains differed with respect to their subgroup specificity.
Acceleration of leukemogenesis in akr mice by grafts, cell suspensions, and cell‐free centrifugates of thymuses from preleukemic akr donors
Authors: Nishizuka Yasuaki , Nakakuki Kazuya
Published: February 2007

Grafting of 5‐month‐old thymuses of AKR mice into young adult AKR and (AKR x SL)F1 recipients shortened markedly the latent period for leukemia development, but thymus grafts from 3‐ and 1‐month‐old AKR mice had no accelerating effect. Transplantation assay of early lymphomas appearing in (AKR x SL)F1 mice revealed that almost all the neoplasms were derived from F1 host cells. Intraperitoneal injections of thymus cell suspensions made from 5‐month‐old AKR mice also caused acceleration of leukemogenesis. Cell‐free centrifugates prepared from 5‐month‐old AKR mouse thymuses had a striking accelerating activity on early development of leukemia when injected intraperitoneally into isologous newborn mice. The centrifugates from 3‐month‐old thymuses had an intermediate activity but the centrifugates from 1‐month‐old thymuses had no activity. The centrifugates made similarly from AKR mouse spleens at various time points during the preleukemic stage did not show accelerating activity. Intrathymic injection of the centrifugates from 5‐month‐old thymuses was more effective in accelerating leukemia development than intraperitoneal injection of the same material.

These results indicate that thymuses of 5‐month‐old AKR mice may contain a large quantity of leukemia viruses and, further, that the latent period may represent the time necessary for the development of an effective concentration of leukemia virus.