bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations in sarcoma and leukemia virus activity in somatic cell hybrids
Authors: Long Cedric , Kelloff Gary , Gilden Raymond V.
Published: February 2007

Somatic cell hybrids have been produced in hypoxanthine‐aminopterin‐thymidine (HAT) selective medium by fusion of mouse cells deficient in hypoxanthine‐guanine phosphoribosyl transferase (HGPRT), shedding Rauscher leukemia virus and a hamster cell deficient in thymidine kinase (TK) carrying the defective murine sarcoma virus (MSV) genome. Clones were isolated that produced sarcoma and leukemia virus at substantially equivalent titers, a 100‐fold excess of sarcoma virus, or just leukemia virus. Eight clones were analyzed by isoelectric fractionation and all found to possess HGPRT and adenosine kinase (AK) of hamster origin. Six of these clones also produced AK characteristic of the mouse parent. The production of excess sarcoma virus by some clones and the lack of sarcoma virus expression in cells possessing hamster genetic material are discussed in terms of integration of sarcoma virus in host‐cell chromosomes.
Australia antigen in Singapore Chinese patients with hepatocellular carcinoma and comparison groups: Influence of technique sensitivity on differential frequencies
Authors: Simons M. J. , Yap E. H. , Yu M. , Shanmugaratnam K.
Published: February 2007

In a previous study using electro‐osmodiffusion, the frequency of Australia antigen (Au) in Singapore Chinese patients with hepatocellular carcinoma (2.6%) was no higher than that in comparison groups. Three possible explanations for the apparent discrepancy between this result and the differentially higher Au frequencies reported by others have occurred to us. The first relates to differences in the sensitivities of the techniques employed for Au detection. A second possibility is that the age distribution of Singapore patients with hepatocellular carcinoma (HCC) may differ from that of patients studied elsewhere. Thirdly, differences in Au frequencies may reflect real biological differences between HCC patients in various countries. In this series, using the more sensitive technique of immune adherence haemagglutination, the frequency of Au in HCC patients (35.3%) was more than four times higher than in any comparison group. These findings indicate that Chinese patients in Singapore have lower Au titres than appear to be present in African patients. The previous failure to detect a higher Au frequency in Singapore HCC patients relative to comparison groups can be explained by the difference in sensitivities of the techniques employed. Whether factors such as ethnic type contribute to geographic differences in the Au titres of HCC patients remains to be investigated.
Feline malignant lymphoma: Environmental factors and the occurrence of this viral cancer in cats
Authors: Schneider Robert
Published: February 2007

Environmental data collected on 221 feline malignant lymphoma cases and age‐, sex‐ and breed‐matched controls were analyzed to find evidence which could prove or disprove a hypothesis of horizontal transmission of feline leukemia virus (FeLV) between cats. The variables studied were divided into three groups: (1) association with other cats; (2) neutering and reproductive experience; and (3) diet, including predatory activities. The analyzed data did not support horizontal transmission of infectious FeLV from cat to cat and the consequential development of malignant lymphoma. Significant differences could not be found for association of case animals with other cats, either within or outside of the household. Secondly, there was no evidence of excess mature non‐neutered cats, particularly males, in the case group. The courtship habits and territorial fights of entire males would dictate that excess of such animals should be present in the case group if horizontal transmission of infectious FeLV occurred. No evidence was found to support the hypothesis that diet, particularly predatory activities, may in some way affect risk. Various hypotheses concerning the pathogenesis of this disease in cats are discussed.
Membrane antigens of human colonic carcinoma and non‐tumoral colonic mucosa: Results obtained with a new isolation method
Authors: Rosai Juan , Tillack Thomas W. , Marchesi Vincent T.
Published: February 2007

A new technique is described for the extraction and purification of the carcinoembryonic antigen (CEA) from human tumors.

This method involves the use of lithium diiodosalicylate for dissociation of the antigen‐membrane complex. The method differs from earlier procedures in that extraction conditions do not rely on an acid precipitation step and that the yield of CEA appears to be approximately 10‐fold greater.

A glycoprotein immunologically similar to CEA was isolated from non‐tumoral human adult colonic mucosa, suggesting that the difference between tumoral and non‐tumoral tissues in this system may be quantitative rather than absolute.
Inheritance of susceptibility to friend mouse leukemia virus. VIII. Effect of a single genetic locus on the pathogenesis of the leukemia
Authors: Odaka Takeshi , Sugano Haruo , Takizawa Kiyoshi
Published: February 2007

The effect of the Fv locus on the pathogenesis of Friend virus‐induced leukemia was studied with two pairs of mouse strains which are congenic except for the locus. The rapid spleen enlargement or spleen focus formation which is characteristic of Friend virus infection occurred in the mice with Fvs/Fvs genotype, DDD and C57BL/ 6‐Fvs. These early responses were not seen in the mice with Fvr/Fvr genotype, DDD‐Fvr and C57BL/6. When the infected Fvr/Fvr mice were observed for 150 days, all of the DDD‐Fvr mice, but none of the C57BL/6, developed splenomegaly. Histological studies of the DDD‐Fvr mice revealed erythroblastic, lymphatic or granulocytic leukemia, or myeloproliferative disorder with a prominent megakaryocyte proliferation. This observation indicates that Friend leukemia virus is able to induce various types of leukemias in mice and the early characteristic responses are completely abrogated in the mice with Fvr/Fvr genotype. Involvement of genetic factor (s) other than the Fv locus in the late‐occurring leukemias was suggested.
Some observations on the epidemiology of cancer of the breast in women of Western India
Authors: Paymaster J. C. , Gangadharan P.
Published: February 2007

The incidence rate for cancer of the breast is comparatively low in India. Cancer of the cervix is more common than cancer of the breast amongst Indian women. Wide variations in the frequency of cancer of the breast have been observed amongst the religious communities of Western India. Compared to other communities, Sindhis (Hindus from Sind) and Parsis (Zoroastrians) have a higher frequency rate for cancer of the breast. It was felt that the prevalence of certain suspected factors may be partly responsible for such variations. Case control studies demonstrated that the role of certain “high risk factors”, especially those related to marriage and pregnancy, could be different in different age groups, and an intensive search for more factors and their significance in different populations and age groups is necessary. The factor or factors which can be used effectively for a public health programme for the prevention of this disease are yet to be demonstrated.
Inhibitors of the bone‐marrow colony formation in sera of patients with leukemia
Authors: Granström M. , Wahren B. , Gahrton G. , Killander D. , Foley G. E.
Published: February 2007

An increased variation of the bone‐marrow colony stimulating factor (CSF) was found in the sera of patients with acute leukemia as compared to normal sera. In sequential samples from the same patient, there was no apparent correlation between changes in the degree of colony stimulating activity and changes in the clinical and hematologic status. CSF levels as measured in untreated sera seemed to depend upon a variation in serum inhibitor levels. After chloroform treatment, sera from patients with acute lymphoid or myeloid leukemias had higher mean CSF activity than similarly treated normal sera, though the variation was considerable in both groups. The increase was most evident in sera which initially exhibited a normal or low degree of colony‐stimulating activity. In order to evaluate CSF in normal persons and in various diseases, it appears important to remove inhibitory substances efficiently, for instance by chloroform treatment.
Cell‐mediated destruction of rous sarcomas in Japanese quails
Authors: Hayami Masanori , Hellström Ingegerd , Hellström Karl Erik , Yamanouchi Kazuya
Published: February 2007

A microcytotoxicity test was used to search for cell‐mediated destruction of sarcomas, induced in Japanese quails by the Schmidt‐Ruppin strain of the Rous sarcoma virus (SR‐RSV).

Spleen cells from quails whose sarcomas had regressed (regressors) were cytotoxic to cultivated Rous sarcoma cells as were, to a lesser extent, regressor thymus cells, while no cytotoxic effect was seen with bursa cells. Autochthonous and allogeneic lymphoid cells from regressors were equally cytotoxic. No cytotoxic effect was seen, on the other hand, with lymphoid cells from quails with growing Rous sarcomas (progressors).

Surgical bursectomy on the day of hatching, which depressed the formation of antibody production to sheep red‐blood cells, led to a higher cytotoxic effect of regressor spleen cells than was seen with cells from non‐bursectomized quails. Spleen cells from thymectomized birds which showed delayed skin graft rejection and had progressively growing rumors were not cytotoxic.

Admixture of progressor spleen cells decreased the cytotoxic activity of normal regressor spleen cells unless the regressors had been bursectomized.
Further studies on mouse sarcoma virus (moloney) replication in human cells. Partial host range shift of progeny virus
Authors: Bernard C. , Chuat J. C. , Laprevotte I. , Boiron M.
Published: February 2007

Several human cell lines were examined for their susceptibility to infection by mouse sarcoma virus, strain Moloney (M‐MSV). Successful transformation was achieved only with concentrated virus from rat cell line 78 Al. The lag time and the extent of cellular alteration were found to be related to the employed multiplicity of infection (total transformation within 4 days at a multiplicity of 0.1). All the experiments performed showed the tropism of the progeny virus (HU‐MSV) to shift from a double murine and human tropism to exclusive human tropism as far as the transforming function is concerned. On the contrary, nontransforming replication in mouse cells was continuously obtained. In vivo studies yielded parallel results: only the leukemogenic potential of HU‐MSV for mice was found to persist. The mechanism of this dissociated host‐range shift of transforming and non‐transforming virions is discussed.
Rous sarcomas induced by heterotransplantation of virogenic rat tumour cells in mice
Authors: Bubeník J. , Barešová M. , Micheel B. , Sovová V. , ElRidi R. , Keclíková M.
Published: February 2007

The virogenic sarcoma RSL was induced in inbred Lewis rats by the Schmidt‐Ruppin variant of Rous virus (SR‐RSV).

Heterotransplantation of RSL cells to newborn C57BL/10Sn mice gave rise to mouse sarcomas in approximately 10% of the recipients. The properties of one of these mouse sarcomas, designated as RSM, were compared with those of the original rat tumour line RSL.

It was found that (1) RSL cells did not contain detectable amounts of infectious chicken, rat or mouse sarcoma virus. However, in contact with permissive chicken fibroblasts the RSL cells produced malignant conversion of avian cells accompanied by the formation of infectious RSV. RSL cells carried a tumour‐associated transplantation antigen (TATA) of Rous sarcomas, a group‐specific (gs) antigen of avian leukoviruses and a membrane antigen (MA), characteristic of Rous sarcomas, detectable by indirect immunofluorescence and cross‐reacting with MA of mouse Rous sarcomas. The MA characteristic of tumours induced by mouse leukoviruses was not detected in the membrane of RSL cells.

(2) RSM cells did not contain detectable amounts of oncogenic avian, mouse or rat viruses in an infectious form. Neither contact of these cells with permissive chicken c/o fibroblasts nor heterotransplantation of RSM tumours to chickens led to malignant conversion of avian cells. Gs antigen of avian leukoviruses was not detectable in RSM cells. However, TATA and MA characteristic of Rous sarcomas were present. Neither MA nor TATA induced by mouse leukoviruses was detected in RSM cells.

The results obtained indicate that the non‐infectious RSV genome present in rat virogenic cells is able to induce tumours in a further mammalian species.
Establishment of continuous lymphoblast cultures from leukocytes of gibbons (Hylobates lar)
Authors: Werner Jürgen , Henle Gertrude , Pinto Carl A. , Haff Richard F. , Henle Werner
Published: February 2007

Efforts were made to establish continuous lymphoblast cultures from peripheral leukocytes of gibbons.
(Hylobates lar).

by co‐cultivation with lethally X‐irradiated human lymphoblasts from Epstein‐Barr virus (EBV)‐producing lines of infectious mononucleosis or Burkitt tumor origins. EBV‐positive lymphoblast lines were derived from all of five animals tested, of which four had no antibodies to EBV‐related antigens and one a marginal level. Growth became evident after an average of 26 days. Several months after injection of autochthonous cultured cells and seroconversion, co‐cultivation again yielded lymphoblast lines, but growth became evident on the average within only 55 days. Separate cultures of the X‐irradiated lymphoblasts or the leukocytes, whether obtained before or long after seroconversion, died within 2–3 weeks. Even during the period of seroconversion only one line became established in numerous attempts without the benefit of co‐cultivation.

Injection of cultured lymphoblasts into the authochthonous animals by different routes failed to induce tumors (or any signs of illness) despite attempted immuno‐suppressive treatment of three of the animals prior to transplantation of the cells. All animals responded with antibody formation to EB viral capsid antigens within 2 to 5 weeks. The time of seroconversion apparently depended upon the percentages of EBV antigen‐containing cells in the cultures. Three animals developed low levels of antibodies to the D component of the EBV‐induced early antigen complex.

Similarities and dissimilarities with results of human leukocyte cultures as well as the implications and deficiencies of these experiments are discussed.
The lymphocyte response to a primary viral neoplasm (MSV) through its entire course in BALB/c mice
Authors: Lamon E. W. , Skurzak H. M. , Klein Eva
Published: February 2007

BALB/c mice injected with Moloney sarcoma virus (MSV) developed tumors within 5–8 days which usually completely regressed by day 20–25. Maximal tumor size was around day 15. Lymphocytes from these animals were examined for activity against target cells bearing the Moloney leukemia virus (MLV) associated cell surface antigen at 2‐ to 5‐day intervals for 30 days. Significantly cytotoxic lymphocytes were obtained from animals which had developed no palpable tumor as early as 2 days after infection and from animals in which tumors had completely regressed. The least active lymphocytes were from tumor‐bearing animals. The cytotoxicity of the active lymphocytes was demonstrated to be antigen‐specific by testing also against target cells which were MLV‐negative.
The formation of variants with a reversion of properties of transformed cells. VIII. in vitro limited life span of variants isolated from tumors
Authors: Rabinowitz Zelig , Sachs Leo
Published: February 2007

Cells transformed after treatment with the chemical carcinogen dimethylnitrosamine (DMNA) inoculated into animals, can produce tumors containing variants with a reversion of in vitro properties of transformed cells. In contrast to variants from tumors produced by polyoma‐transformed cells, 83% of the variants in tumors from DMNA‐transformed cells had again acquired, like normal cells, a limited life‐span. in vitro. Seventeen % of the variants escaped the termination of their life‐span by re‐reverting to the transformed state.
Étude expérimentale de la diffusion métastatique chez l'œuf de poule embryonné. Répartition, microscopie et ultrastructure des foyers tumoraux
Authors: Vlaeminck M. N. , Adenis L. , Mouton Y. , Demaille A.
Published: February 2007

The injection of mouse ascite Ehrlich carcinoma cells into a vein in the chorioallantoic membrane of chick embryos at the eleventh day of incubation permits the observation of tumoral focuses analogous to metastasis in intra‐ or extraembryonic viscera, in 70% of embryos, dead or killed between the seventeenth and the twenty first day of incubation. A very clear selectivity can be observed in the invasion of the different organs by the carcinoma cells. The liver is injured most, with a level of metastasis of about 25%, while the spleen is almost never injured. Between these two extremes are ranged the brain, heart, nephros and lungs. The frequency of tumoral nodules in the chorioallantoic membrane, and the richly vascularized mesenchymatous structure of this organ allows for some aspects of tumoral invasion to be analyzed, particularly the relationship between cancer cells and blood vessels. As shown by electron microscopy, the passage of the cancer cells through the capillary barrier is achieved successively by apposition to the outer wall of the vessel, distribution of the basal membrane, endothelialisation and then immediate embolisation without associated thrombosis.
Carcinogenicity of contaminants in indigenous edible oils
Authors: Ranadive Kamal J. , Gothoskar Sunanda V. , Tezabwala Bilquis U.
Published: February 2007

Edible oil is one of the essential constituents of Indian diet which has to be free of hazardous contaminants. A variety of oils are used in different parts of the country, e.g. ground‐nut oil, mustard oil, coconut oil, sesame oil, etc. A series of ground‐nut oil, mustard oil and soya‐bean oil samples have been tested for carcinogenicity due to possible contaminants: (i) solvent residues and (ii) argemone oil. The experiments are divided into two parts: I. Testing the carcinogenicity of solvent‐extracted edible oils, and II. Testing carcinogenicity due to argemone oil. Two strains of mice, inbred C17‐specially developed for testing environmental carcinogens‐and inbred Swiss from the Cancer Research Institute, have been used as test animals. Three routes of administration have been used: (i) cutaneous application, (ii) single and multiple subcutaneous injections and (iii) oral feeding by stomach tube.

I. Solvent‐extracted oils: The results of testing experiments in 1966 indicate the carcinogenic effect of many indigenous solvent‐extracted ground‐nut oil samples as against machine‐expressed oils and imported soya‐bean oils that are mostly free of carcinogenic effect. The second batch of ground‐nut oil samples tested in 1969 after change of solvent to proper food‐grade n‐Hexane show significant improvement.

II. Effect of argemone contamination: Pure laboratory‐expressed argemone oil, diluted in different concentrations in (i) imported soya‐bean oil, (ii) authentic expressed mustard oil and (iii) market tinned oil, as well as pure argemone oil control and other solvent controls, have been tested for carcinogenicity. The data indicate that argemone oil by itself is not carcinogenic at the dose levels tested. In combination with non‐carcinogenic soya‐bean oil and authentic mustard oil also it had hardly any carcinogenic effect. On the other hand, the market sample of tinned mustard oil was weakly carcinogenic by itself; the carcinogenic effect is significantly enhanced by addition of argemone oil at the 1 and 2% level. The data suggest that argemone oil has a co‐carcinogenic effect and the market sample of mustard oil possibly contains weakly carcinogenic principles other than the argemone oil. These observations invite further investigations on market samples of edible oils.
Toxic effect of 7,12‐dimethylbenz‐α‐anthracene on neoplastic cells grown in mixed cultures with normal fibroblasts
Authors: Mittelman L. A. , Sharovskaya Ju. Ju. , Vasiliev Ju. M.
Published: February 2007

Neoplastic L fibroblasts grown in isolated cultures are highly resistant to the toxic effects of carcinogenic hydrocarbons. However, these cells become very sensitive to the toxic effect of 7,12‐dimethylbenz‐α‐anthracene (DMBA) if they are grown on the surface of the monolayer of normal mouse fibroblasts. The density of L cells grown on the glass surface in the same mixed cultures was not significantly changed by DMBA. L cells seeded in the culture of normal fibroblasts 3 days after the removal of DMBA from the medium were not damaged. These experiments indicate that normal fibroblasts exposed to DMBA transmit some toxic factor to L cells placed in their immediate vicinity. It is suggested that this factor may be some short‐lived metabolite of DMBA formed within the normal cells. It is possible that such a “lethal metabolic cooperation” with normal cells may considerably change the sensitivity of neoplastic elements in vivo to various toxic substances.
Cellular and humoral immunity to rat hepatoma‐specific antigens correlated with tumour status
Authors: Baldwin R. W. , Embleton M. J. , Robins R. A.
Published: February 2007

Lymphocytes from rats bearing primary or transplanted aminoazo‐dye‐induced hepatomas were specifically cytotoxic for cells of the same tumour. Cytotoxic antibody was not present in the serum of these animals, although humoral factors capable of abrogating lymph‐node cell‐mediated cytotoxicity in vitro were detected. Following excision of transplanted hepatomas, cytotoxic lymph‐node cells were still demonstrable, with slightly increased reactivities comparable to those detected in a previous study of repeatedly immunized rats. Cytotoxic antibody was present in serum after tumour excision, and this correlates with the loss of serum blocking activity for lymph‐node cell‐mediated cytotoxic effects. In comparison, serum from rats repeatedly immunized to hepatomas, where high levels of cytotoxic antibody are also present, blocks lymph‐node cell‐mediated reactions in vitro, despite the immune status of the donor. These considerations suggest qualitative differences between the blocking factors in the serum of tumour‐bearer and tumour‐immune hosts, the former being antigen‐antibody complexes, and the latter free antibody.
Failure to demonstrate immunity to leukemia associated antigens by lymphocyte transformation in vitro
Authors: Schweitzer Marjan , Melief C. J. M. , Eijsvoogel V. P.
Published: February 2007

Mixed cultures of leukemic cells from acute lymphatic leukemia patients with autologous remission lymphocytes and of leukemic cells from both acute lymphatic leukemia patients and chronic lymphocytic leukemia patients with the lymphocytes from an HL‐A identical sibling were performed to investigate whether sensitization against leukemia‐associated antigens was demonstrable. Although in some cases marked thymidine incorporation was measured, this cannot be interpreted as stimulation by leukemia‐associated antigens, because it cannot be distinguished from non‐specific thymidine incorporation as was shown to occur sometimes in unstimulated cultures. It is concluded that the lymphocyte transformation technique is unsuitable for the detection of immunity to leukemia‐associated antigens.
Fine structure of pituitary tumors and transplants in mice: Effects on the prostate
Authors: Petrea I. , Gardner W. U.
Published: February 2007

Twenty‐seven primary pituitary tumors (PPT) arose in 109 mice bearing transplanted pituitary glands (TPG). Several PPT were transplanted serially into isologous hosts. Transplanted pituitary tumors (TPT) from 79 different male or female hosts were obtained between 42 and 708 days after transplantation. Histological and electron microscopic preparations of the TPG, PPT and TPT were prepared. The TPG showed much cellular necrosis and diminished secretory activity during the first month. Cellular replacement and secretory granules reappeared after revascularization of the grafts and coincident with the reappearance of somatotrophic and mammotrophic activity in the female hosts. The TPG showed no significant growth for about 1 year and about 25% of the transplants became tumorous after 400 days. EM examination of the PPT revealed heterogeneous secretory granules resembling those of the alpha and beta type in the same cell. The endoplasmic reticulum (ER) was abundant and the mitochondria were large and many were structurally abnormal. The TPT usually grew slowly but differed from tumor line to tumor line. By six months after transplantation the TPT were polynodular, with red nodules and white nodules. In both red and white tumoral nodules, the cells were PAS, reticulin, amyloid, elastin and Masson‐negative, and showed some autoradiographic activity after proline‐H3 administration. Also, the EM shows no significant difference between the nodules. Fibrils about 70 Å in diameter were in the ER, and 100–300 Å in diameter in plasma fundamentalis, and fibers larger than 300 Å in extracellular areas. The fibrillar synthesis in the TPT cells was in inverse ratio to the granular secretory activity of the cells. Sixteen of the TPT in CB 815 and 87 hybrid mice contained C‐type virus‐like particles (VP). Viral particles were noted in the periphery of the nucleus, and in the endoplasmic reticulum. Cells with the most viral particles showed the least granular secretory activity. The TPT in females were mammotrophic, and in males prostatotrophic. The prostatic epithelial cells contain cytoplasmic organelles with delicate lamellae in fingerprint, whorl, or tubular arrangement and amorphous granular aggregates. Mice with TPT for several months had enlarged prostates, some having intraluminal hyperplastic trabeculae, and cells showing less secretory activity. In mice with two lines of TPT, C‐type viral particles appeared in the prostatic cells.
Establishment of multiple lymphoblastoid lines from single lymph nodes and study of their immunoglobulin synthesis
Authors: Béchet J. M. , Nilsson K. , Pontén J.
Published: February 2007

Biopsies of one normal lymph node and two lymphomas were explanted into a number of independent cultures. Lymphoblastoid lines were established from a high proportion of the cultures from each biopsy. The immunoglobulins synthesized by each line were characterized and used as cell markers in an attempt to obtain information on the cellular origin of the lines. The majority of the lines produced, at the beginning of their culture history, several types of heavy and light chains, but this pattern evolved in the course of cultivation towards the production of only one species of immunoglobulin. Lines from the same lymph node differed from each other by the types of immunoglobulins produced, both initially and at a later stage. The results suggest that lymphoblastoid lines are derived from a non‐clonal population of precursor cells, and argue against the neoplastic nature of these cells.
Secretory and mitotic response of the male rat pituitary gland to repeated doses of oestrogen
Authors: Lloyd H. M. , Meares J. D. , Jacobi Joan
Published: February 2007

Pituitary weight, pituitary mitotic index and pituitary and serum concentrations of growth hormone and prolactin were measured at 14‐day intervals in male rats given 10 mg diethylstilboestrol dipropionate SC every 14 days for a total period of 70 days. Mean pituitary weight reached a maximum of 21 mg on day 42 and no pituitary gland became a tumour according to a criterion of weight greater than 30 mg. Mitotic index was greatly increased until day 70 when it diminished significantly. Pituitary concentration of growth hormone decreased to maintain a low constant level from day 28 onwards while pituitary prolactin concentration rose to a maximum on day 42. Serum growth hormone was elevated on day 14 and then gradually diminished, while serum prolactin continued to increase until day 42. Pituitary weight and serum prolactin were significantly correlated and pituitary mitotic index was negatively correlated with pituitary growth hormone concentration. The state of apparent equilibrium in mass reached by the pituitary glands from day 42 until day 70, despite greatly increased secretory and mitotic activity, suggests that further disturbance of pituitary function is necessary to bring about net gain in cell numbers and lead to tumour formation.
Effect of human placental lactogen on growth of carcinogen‐induced mammary tumors in rats
Authors: Nagasawa Hiroshi , Yanai Reiko
Published: February 2007

The effect of exogenous administration of human placental lactogen (HPL) on 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced mammary tumors was studied in female Sprague‐Dawley rats. Twice daily injections of 1 or 2 mg HPL for 20 days showed marked stimulation of appearance and growth of mammary tumors and of normal mammary gland growth not only in intact but also in adreno‐ovariectomized rats. These results suggest that placental lactogen plays an important role in the growth of DMBA‐induced mammary tumor of rat and that it acts on mammary tumorigenesis during pregnancy both directly and indirectly through its promotion of progesterone secretion by the ovary.
Specific “arming” of normal lymph‐node cells by sera from tumor‐bearing mice
Authors: Pollack Sylvia
Published: February 2007

Lymph‐node cells of non‐sensitized mice were “armed” (i.e. made specifically cytotoxic) by exposure in vivo to passively transferred sera from tumor‐bearing mice. Four hours after an intraperitoneal injection of antitumor serum, the lymph nodes were removed from recipient mice and the activity of the lymph‐node cells was tested on tumor cells in an in vitro microcytotoxicity test. Specific cytotoxicity was demonstrated to the respective target tumors (Moloney virus or 3‐methylcholanthrene‐induced sarcoma) carried by the tumor‐bearing serum donors.
The effects of neonatal thymectomy on the antitumour activity of lentinan, carboxymethylpachymaran and zymosan, and their effects on various immune responses
Authors: Maeda Yukiko Y. , Chihara Goro
Published: February 2007

The mechanism of antitumour action of the polysaccharides, lentinan and carboxymethylpachymaran, was examined and compared with that of zymosan. It was revealed that (1) these polysaccharides did not show any direct cytocidal effect on tumour cells; (2) these polysaccharides had no antitumour action at all in neonatally thymectomized mice, indicating the important role of the thymus gland in tumour regression; and (3) in spite of these facts, these polysaccharides, contrary to zymosan, did not accelerate various conventional immune responses such as phagocytic activity, antibody production against heterologous antigen, increased number of peripheral lymphocytes, skin homograft rejection, and delayed hypersensitivity. This evidence suggests the presence of a complex and unknown mechanism for regression of transplanted tumour in the action of lentinan and carboxymethylpachymaran.
Leukemia induction in C3H mice following their inoculation with normal AKR lymphoid cells
Authors: Nemirovsky Theodore , Trainin Nathan
Published: February 2007

Newborn C3H mice were injected with viable or in vitro X‐irradiated cell suspensions from lymph node and spleen mixtures obtained from healthy AKR donors aged 12 to 18 months. Of the group injected with normal intact cells, 30% developed a lymphocytic leukemia, whereas none of the recipients of irradiated cells did so. Genetic analysis showed that the leukemias appearing in C3H mice originated de novo in the recipient animals apparently as a result of their inoculation with immunocompetent lymphoid cells. The results obtained by using this model of leukemia induction are discussed on the basis of participation of a graft‐versus‐host reaction in this process.
Immune responses in mice to tumour challenge after immunization with newcastle disease virus‐infected or X‐irradiated tumour cells or cell fractions
Authors: Beverley P. C. L. , Lowenthal R. M. , Tyrrell D. A. J.
Published: February 2007

Cells of the transplantable ascites tumour sarcoma 37 (S37) have been infected in vitro with Newcastle disease virus (NDV). Infected cells, a virus‐containing fraction of such cells, and X‐irradiated S37 cells have been found to immunize mice against subsequent tumour challenge. Anti‐lymphocyte serum and anti‐theta serum interfered with this immune response. The level of humoral anti‐tumour antibody did not correlate with immunity. Preimmunization with homologous virus (NDV) prior to inoculation with a virus‐containing tumour cell fraction did not in this system enhance the immune response against tumour challenge. The implications of these findings are discussed. Caution is advocated in applying the results of experiments with such animal tumour virus models to the human clinical situation.
In vitro interference between low and high leukaemogenic variants of rauscher virus
Authors: Boyd Rosemary E. , Youn Jung Koo , Barski Georges
Published: February 2007

Cultures of the virus‐free P4bis line, originating from a C57B1 mouse, were infected in vitro with a “low leukaemogenic” variant (RC) of the Rauscher leukaemia virus (RV), prepared from long‐term cultures of this virus in syngeneic cells. Later, after different delays, these infected cultures (P4bis + RC) were superinfected with a highly pathogenic variant (RR) of the RV, obtained from short‐term cultures of RV extracted from spleens of leukaemic mice. Eighteen days after these superinfections with RR, supernatants of the doubly‐infected cell cultures (P4bis+RC+RR) and their corresponding controls were assayed for leukaemogenic potential by intraperitoneal inoculation into young adult BALB/c mice. The proportion of mice which had developed leukaemia by the 120th day after inoculation served for the evaluation of in vitro interference between the RC and RR virus variants. Even when the in vitro infection of cells with RC virus was followed only 1 h later by the RR superinfection, there was a significant difference between the proportion of leukaemic animals in the group inoculated with P4bis+RC+RR supernatant (56%) and that in the P4bis+RR positive control group (88%). With intervals of 12 days or 21 days between the two in vitro viral infections, the drop in leukaemogenicity of the doubly‐infected cultures became more accentuated; the longer the time interval, the greater was the interference effect. Indirect immunofluorescence tests made at intervals after infection of P4bis with RC showed a steady increase in the percentage of RV antigen positive cells up to the 3rd week after infection. The mechanism of the observed interference is discussed, and it is suggested that a straight relationship exists between the spread, horizontal and/or vertical, of the RC virus infection in the cultures and the blocking of their superinfection by the highly pathogenic RR virus.
Antibodies to Epstein‐Barr virus and cellular immunity in Hodgkin's disease and chronic lymphatic leukemia
Authors: Hesse J. , Andersen E. , Levine P. H. , Ebbesen P. , Halberg P. , Reisher J. I.
Published: February 2007

Antibodies to Epstein‐Barr virus capsid antigen (VCA), early antigen (EA) and cellular immunity as measured by skin reactivity to keyhole limpet hemocyanin (KLH) and Brucella antigen (BA) were measured in 15 cases of Hodgkin's disease (HD) and 14 cases of chronic lymphatic leukemia (CLL) before treatment and one year later. Both groups of diseases were associated with elevated VCA and EA antibody levels when compared with 18 controls, and in both groups the mean titers were unchanged after therapy. A negative skin test to KLH was associated with a short survival in the HD group and was found more frequently in CLL patients with active disease. In the young HD patients, a higher EBV titer was found in pretreatment sera of non‐survivors compared with those who are still alive. There was no correlation, however, between tests for cell‐mediated immunity and humoral antibodies against EBV. The finding of similar titers in patients with depressed and normal skin reactivity indicates that the elevated titers are probably not the result of a non‐specifically depressed immune defense.
Cell‐mediated and serum blocking reactivity to tumor antigens in patients with malignant melanoma
Authors: Heppner G. H. , Stolbach L. , Byrne M. , Cummings F. J. , McDonough E. , Calabresi P.
Published: February 2007

The reactivity of human lymphocytes, separated from peripheral blood by procedures involving sedimentation through plasmagel and settling on a glass surface, on survival or growth of melanoma tumor cells is reported. Assay of reactivity was by either a colony inhibition in dilute agar (GEL) technique or a microcytotoxicity assay (MC). In 54 experiments with lymphocytes from normal donors, inhibition of melanoma cell viability, as compared to growth in medium alone, was seen 25 (46.3%) times, stimulation was observed seven (12.9%) times and no effect 22 (40.7%) times. These results were not influenced by matching of the lymphocyte and tumor‐cell donor for ABO blood group. Inhibition was seen less often, however, in tests with the GEL method than in those with the MC assay. Eighty‐two experiments assessed the effect of lymphocytes from melanoma patients on melanoma cell viability. Inhibition to an extent greater than that of normal lymphocytes tested at the same time was seen 65 (79.3%) times. There was no difference in the frequency of detection of inhibition with lymphocytes from patients with local, regional, or widespread disease, although the percentage inhibition was less in the latter group. No differences were seen between patients with clinically active versus inactive disease. Only one of five patients who were within a week of death was reactive. Reactivity was detected as frequently with allogeneic as with autochthonous melanoma target cells. Serum blocking factor (SBF), capable of inhibiting in vitro cell‐mediated reactivity to melanoma tumor cells, was assayed in serum from melanoma patients at various stages of disease. SBF was detected at some time in 30% of patients with local, 88.9% with regional, and 80.0% with widespread disease. It was found in 42.9% of those with clinically inactive and 70.6% with active melanoma. However, detection of SBF was found to fluctuate from sample to sample taken at different times during the course of disease in individual patients regardless of clinical status. The importance of sequential determinations of SBF activity for patient assessment is stressed.
Treatment of a mouse lymphoma by L‐asparaginase: Success depends on the host's immune response
Authors: Carter R. L. , Connors T. A. , Weston B. J. , Davies A. J. S.
Published: February 2007

Regression of the L‐asparaginase‐sensitive Gardner lymphosarcoma was investigated in normal CBA mice and in CBA mice deficient in thymus‐processed lymphocytes (T cells). In normal animals, solid subcutaneous grafts of the tumour disappeared completely following one intraperitoneal injection of L‐asparaginase (50 IU) given 10 days after tumour inoculation. The local tumour was impalpable after 3 or 4 days and there was early and massive destruction of the graft though surviving tumour cells persisted in the vicinity of blood vessels for up to 24 h after treatment. These cells subsequently disappeared and there was an intense local inflammatory response dominated by macrophages. In mice deficient in T cells, the Gardner lymphosarcoma initially regressed as in the normal group but the small perivascular accumulations of surviving tumour cells did not disappear; they persisted and all the animals eventually died with local and disseminated lymphosarcoma 22–24 days later. Their recurrent tumours were invariably asparaginase‐resistant. These results indicate that, although the main effect of L‐asparaginase is the biochemical destruction of sensitive tumour cells, residual asparaginase‐resistant cells are normally destroyed by the host's immune response. In T‐cell‐deficient mice, the immune component does not operate effectively and asparaginase‐resistant tumour cells grow back and kill the animals. T cells appear to be involved in the immune response to the Gardner lymphosarcoma and some possible modes of action of T cells are discussed.
Contribution of host immunity to cyclophosphamide therapy of a chemically‐induced murine sarcoma
Authors: Moore Michael , Williams Dorothy E.
Published: February 2007

The contribution of host immune factors to the therapeutic effect of cyclophosphamide (CPA) on an antigenic chemically‐induced sarcoma (MCA‐2) transplanted in syngeneic mice with different immunological reactivity was investigated. In non‐sensitized mice, CPA failed to prevent survival of nascent tumour emboli comprising 105 cells. By contrast, the enhanced therapeutic efficiency of CPA against clinically detectable neoplasms or nascent tumours developing progressively from small inocula (104 cells) suggested that host sensitization may play a role in cyclophosphamide‐mediated regression of this tumour. The hypothesis was investigated by comparison of the effect of CPA treatment on palpable neoplasms growing in immunodepressed mice following wholebody irradiation (400 R) and specifically immunostimulated mice which had received irradiated (15,000 R) MCA‐2 cells, with their untreated immunocompetent counterparts. In the first group, the antitumour effect of CPA was noticeably weaker compared with that observed in normal mice, while in the second, the effect was markedly potentiated, so that palpable nodules comprising in excess of 5 × 106 cells underwent complete regression. Since the maximum level of resistance evoked by sarcoma MCA‐2 per se was of the order of 2 × 105 cells, the results indicate that pre‐immunization significantly augments the antitumour activity of CPA in this system. The specificity of the reaction was demonstrated by the failure of CPA to mediate complete regression of sarcoma MCA‐2 growing in mice previously immunized with normal muscle or an antigenically unrelated neoplasm (MCA‐7). Possible mechanisms for the synergistic activity of CPA and host immune factors in this tumour‐host system are discussed.
Oncogenic activity of N‐nitrosododecamethyleneimine in liver, glandular stomach and other tissues of NZO/B1 mice
Authors: Goodall C. M. , Lijinsky W. , Keefer L. , D'ath E. F.
Published: February 2007

N‐nitrosododecamethyleneimine (NDMI), a new member of the alicyclic nitroso imine series, was synthetized and tested in NZO/Bl mice, as part of structure‐activity studies. Treated mice had significant incidences of liver and glandular stomach tumors, thought to represent the characteristic oncogenic activity of NDMI. There were also statistically significant increases in tumors of lung, duodenum and reticular tissues, but these tumors were common in controls. By contrast with the strong carcinogenic activity of lower members of the series towards pharynx and esophagus, NDMI produced no lesions at these sites. A synthesis for NDMI is given.
Distribution of basic azo‐dye‐binding protein in normal rat tissues and carcinogen‐induced liver tumors
Authors: Bannikov G. A. , Guelstein V. I. , Tchipysheva T. A.
Published: February 2007

Monospecific antibodies against basic azo‐dye‐binding protein from the rat liver were obtained. An antigen identical to this protein was shown to be present in the liver, kidney, small intestine, ovary and testicle extracts of rats and also in liver and kidney extracts of mice. The concentration of this antigen was significantly reduced in the liver and kidney of rat embryos and in rats during the early postnatal period. Immuno‐fluorescence technique was employed to study distribution of the azo‐dye‐binding protein in sections of normal rat liver and liver tumors induced by 3′ ‐methyl‐4‐dimethylami‐noazobenzene. This protein was found in the hepatocytes of the central areas of the acinus but not in the hepatocytes of periportal zones. The azo‐dye‐binding protein was absent from poorly‐differentiated hepatomas, anaplastic carcinomas and from most adenocarcinomas. In all the highly‐differentiated hepatomas this protein was found to be uniformly distributed among the tumor cells. Thus the presence of azo‐dye‐binding protein in tumors seems to depend on the degree of cell differentiation.
Metabolism of the carcinogenic hydrocarbon benzo(a)pyrene in human fibroblast and epithelial cells
Authors: Huberman Eliezer , Sachs Leo
Published: February 2007

Metabolism of the carcinogenic hydrocarbon benzo(a)pyrene (BP) to water and alkali‐soluble products was measured in cultured fibroblast and epithelial cells from human embryos. The alkali‐soluble products represented only a small fraction of BP metabolism. Fibroblasts from different organs from the same embryo metabolized similar amounts of BP, while those derived from different embryos can metabolize different amounts. The fibroblasts were divided into three groups which metabolized an average of 350, 850 and 3,400 μμmoles of water soluble products/106cells/3 days. No significant differences were found in relationship to the age of the embryos from 2.5 to 5 months. Fibroblasts from the endometrium of adult women metabolized less than embryonic fibroblasts. Cultures which contained more than 20% epithelial cells metabolized 3–25 times more BP than fibroblast cultures from the same embryo. Epithelial cells from different embryos also varied in the degree of BP metabolism and low epithelial activity was not necessarily associated with low fibroblast activity in the same embryo. It is suggested that there is a genetic heterogeneity in BP metabolism in fibroblast and epithelial cells, and that the higher activity of epithelial cells might be related to the higher incidence of carcinomas rather than sarcomas in humans.
In vivo and in vitro binding of carbon tetrachloride with nucleic acids and proteins in rat and mouse liver
Authors: Rocchi P. , Prodi G. , Grilli S. , Ferreri A. M.
Published: February 2007

14C‐labelled carbon tetrachloride binds in vivo to DNA of mouse liver and to rRNA of rat liver if the animals have been pretreated with 3‐methylcholanthrene. A noticeable amount of radioactivity is also observed in liver proteins. In vitro carbon tetrachloride is activated by microsomes and pH 5 enzymes of 3‐methylcholanthrene‐treated animals to a metabolite which can react with DNA and polynucleotides; this effect is more evident if subcellular fractions from mouse liver are used.
Effect of 4‐N‐benzyldemethylrifampicin and of radiation therapy on rauscher viral leukemia in vivo
Authors: Okunewick James P. , Phillips Eleanore L. , Erhard Penny
Published: February 2007

Studies were carried out to evaluate the therapeutic effects of 4‐N‐Benzyldemethylrifampicin (AF/ABP) and of radiation on the survival of mice infected with Rauscher leukemia virus (RLV). To assess this effect two parameters were employed. These were (a) the percentage of animals surviving 6 months after infection, and (b) the average survival time of the animals which died. The results indicate that administration of the drug shortly after virus resulted in a marked increase in the number of survivors, but without any lengthening of survival time among the animals which died of the leukemia. Administration of the drug 14 days after virus had no beneficial effect on either survival time or number of survivors. The effect of radiation 14 days after virus infection significantly increased the survival time, but did not materially affect the ultimate number of survivors at 6 months after the virus infection. Combined employment of radiation and the drug 14 days after viral infection did not show any significant improvement over the use of radiation alone. Reduction of viral leukemia‐related splenomegaly was also noted following both radiation treatment and drug treatment. However, no significant correlation could be drawn between this reduction in splenomegaly and the survival time or the number of survivors.