bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous expression of murine endogenous viruses in hamster X mouse hybrid cells
Authors: Park Sang S. , Gazdar Adi F. , Lalley Peter A. , Minna John D. , Francke Uta
Published: February 2007

The spontaneous expression patterns of murine leukemia virus (MuLV) from mouse spleen cultures and hamster × mouse spleen hybrid cells were compared. The hybrid cells preferentially segregated mouse while retaining a complete set of hamster chromosomes. Virus expression patterns showed considerable mouse strain differences in both parental and hybrid cells. None of 13 BALB/c spleen cultures expressed virus while 6 of 20 hybrid clones expressed N‐tropic or N‐tropic and X‐tropic viruses. All AKR spleen cultures and 5 of 7 hybrids expressed N‐tropic but not X‐tropic virus. X‐tropic virus expression was detected in all 6 NZB spleen cultures and in 5 of 8 hybrids. Virus expression did not occur in NIH Swiss or NIH Swiss/Nude (nu/nu) spleen or hybrid cultures. A major structural locus (Akv‐1) for N‐tropic virus expression has been assigned to chromosome 7 in AKR mice by recombi‐national genetics and is closely linked to the gene for glucose phosphate isomerase (Gpi‐1). Analysis of AKR hybrids confirmed the requirement of chromosome 7 for initial expression of mouse N‐tropic virus and, in addition, excluded the role of all other mouse chromosomes in this phenomenon. Eighteen of 20 BALB/c clones retained chromosome 7, including 6 virus‐positive clones, suggesting that chromosome 7 may be necessary but is not sufficient for N‐tropic virus expression in this strain. Hybrid clones with examples of asynteny were found for all other chromosomes. Long‐term passage and sub‐cloning studies of AKR and BALB/c virus‐positive hybrids indicated that virus‐positive clones segregated independently of chromosome 7 markers. Spontaneous expression of X‐tropic virus in NZB hybrid clones was syntenic with the gene for‐enylate kinase (Ak‐1) which is assigned to chromosome 2. A relatively small number of NZB hybrid clones were studied and, a firm gene assignment cannot be made, because only one discordant clone each was found for chromosomes 1, 3, 10, 19. Our studies indicate that spontaneous expression of MuLV strains does not require the following MuLV‐related genes: Fv‐1 (chromosome 4), Fv‐2 (chromosome 9), Rec‐1 (replication of ecotropic virus, chromosome 5), Gv‐1 and H‐2 (chromosome 17).
Biochemical identification of primate lymphoid cell‐surface glycoproteins
Authors: Strnad Bruce C. , Neubauer Russell H. , Rabin Harvey
Published: February 2007

We have employed the galactose oxidase‐tritiated sodium borohydride labelling method to examine the surface glycoproteins of cotton‐topped marmoset and other primate cell lines either established from tumors or transformed in vitro by different lymphotropic herpesviruses. The labelled surface glycoproteins were separated on acrylamide gels in the presence of sodium dodecyl sulfate (SDS) and analyzed by fluorography. Our results indicate that (1) lymphocytes of the same class from different primate species are similar but can be distinguished; (2) T and B lymphocytes of the same species can be differentiated; (3) cotton‐topped marmoset lymphocytes of the same class show marked similarities regardless of tumor or in vitro origin or virus used for transformation; (4) three cell lines established from different EBV‐induced tumors of the same marmoset show essentially the same labelling pattern, supporting the hypothesis that they originated from a single clone.
The effects of hyalurodinase upon tumor formation in BALB/c mice painted with 7,12‐dimethylbenz‐(a)anthracene
Authors: Pawlowski Andrew , Haberman Herbert F. , Menon I. Aravindakshan
Published: February 2007

Experiments were performed to investigate the effects of hyaluronidase on chemical carcinogenesis. Two experiments were carried out using BALB/c mice. In the first experiment the mice were divided into three groups, viz. (1) painted with 7, 12‐dimethyl‐benz(a)anthracene (DMBA), (2) injected with hyaluronidase and painted with DMBA and (3) injected with saline and painted with DMBA. In the second experiment the mice were divided into three groups: (1) painted with DMBA, (2) injected with hyaluronidase and painted with DMBA and (3) injected with heat‐inactivated hyaluronidase and painted with DMBA. The tumor incidence and size of tumors were significantly lower in the group treated with hyaluronidase than in the other groups. The latent period was increased. The mitotic index of the skin adjacent to the tumors at the end of the experiment was decreased. These studies show that hyaluronidase can act as an anticarcinogenic agent.
Induction of erythroid differentiation in murine erythroleukemia cells by N‐substituted polymethylene diamides
Authors: Hozumi Toyoharu , Nomura Junko , Ishizawa Minoru
Published: February 2007

Various N‐substituted polymethylene diamides were synthesized and tested for their potency to induce erythroid differentiation in murine erythro‐leukemia cells. N,N,N′,N′‐tetramethyl‐1.6‐hexane‐dicarboxamide (IIc) was the most potent inducer among 15 compounds tested. The effectiveness of this compound was similar to that of hexamethylene bisacetamide(HMBA). HMBA has a different amide linkage order from that of IIc. HMBA and IIc at a concentration of 5 mM had similar effects on the cell growth rate and induced a similar frequency of benzidine‐positive cells. Hower, hemoglobin production was 1.5 times more effective with IIc. Polymethylene diester, diamide, dihydrazide and dianilide had no effect on the induction of hemoglobin synthesis. The N‐alkylated amide group appears to be required for induction of differentiation in murine erythroleukemia cells.
Characterization of a leukemic cell line of the pre‐B phenotype
Authors: Hurwitz Richard , Hozier John , Lebien Tucker , Minowada Jun , Gajl‐Peczalska Kazimiera , Kubonishi Ichiro , Kersey John
Published: February 2007

NALM‐6‐M1, one of eight leukemia cell lines cultured from the blood of a 19‐year‐old boy with non‐T, non‐B acute lymphoblastic leukemia (ALL) in relapse, was characterized. This cell line was found to be more than 90% cytoplasmic Immuno‐globulin positive (clg+) for both mu heavy and lambda light chains, but surface immunoglobulln (slg) and complement receptor (CR) negative. NALM‐6‐M1 was clg∼ for alpha, delta, and gamma heavy chains and kappa light chain. About 45% of the cells exhibited sheep erythrocyte receptors. Approximately 12% of cells were positive for Fc receptors. Approximately 90% of the cultured cells had a deleted long arm of chromosome 5 (5q−) and a marker Y chromosome. The remaining 10% of cells were found to have some additional chromosomal material on the long arm of chromosome 12, suggesting a partial translocation. No other karyotypic abnormalities were found. The cell line was found to react strongly with anti‐p23, 30, suggesting la‐like activity, but it only weakly stimulated normal lymphocytes in mixed leukocyte culture (MLC). The cells expressed HLA antigens. NALM‐6‐M1 failed to react with anti‐thymocyte serum (ATS), did not possess Epstein‐Barr membrane or nuclear antigens, nor did it exhibit phagocytosis for zymosan. NALM‐6‐M1 reacted positively with oil red O and Sudan black stains. On the basis of the clgM staining, NALM‐6‐M1 seems to be arrested at an early stage in B‐cell development and is considered to be of the pre‐B cell phenotype possessing a chromosomal abnormality.
Antibody responses to herpesvirus papio antigens in baboons with lymphoma
Authors: Neubauer Russell H. , Rabin Harvey , Strnad Bruce C. , Lapin Boris A. , Yakovleva Lelita A. , Indzie Eleonor
Published: February 2007

An Epstein‐Barr virus‐related herpesvirus, termed Herpesvirus papio (HVP), was isolated from baboons (Papio hamadryas) at the Institute of Experimental Pathology and Therapy, Sukhumi, USSR, where there is a continuing outbreak of lymphoma. In the present study sera from diseased baboons and from age‐and sex‐matched control animals were examined for antibodies to HVP antigens. Results showed that animals with lymphoid disease had antibodies to HVP virus capsid, early, soluble, and nuclear antigens at higher frequencies and at higher titers than did control animals. Antibody titers were nat age‐or sex‐related. No concordancy was detected for antibodies to soluble and nuclear antigens. The sera were also examined for antibodies to two other widely distributed viruses of hamadryas baboons, cytomegalovirus and foamy virus. The results of these studies did nat indicate a disease‐related role for either of these viruses.
Differences in EBV receptor concentration between in vitro EBV‐converted lymphoma sublines reflect biological differences between the converting viral substrains
Authors: Klein George , Manneborg Agneta , Steinitz Michael
Published: February 2007

We have compared the EBV‐receptor concentration of two originally EBV‐negattve human B‐cell lymphoma lines, after in vitro conversion with the transforming B95‐8 or the cytopathic P3HR‐1 EB‐viral substrain, respectively, into permanent EBV‐carrying sublines. Receptors were measured by the quantitative EBV‐absorption bioassay of Sairenji and Hinuma (1973). EBV receptor concentration of all P3HR‐1 virus‐converted sublines was significantly reduced, in comparison with the B95‐8 virus‐converted sublines. This suggests that cells with a low receptor concentration are more likely to survive the initial infection with the P3HR‐1 viral harvest. The results further confirm the biological differences between the two EBV substrains.
Neoplasms in rats and mice fed butylurea and sodium nitrite separately and in combination
Authors: Murthy A. S. Krishna , Baker John R. , Smith Emil R. , Zepp Ellen
Published: February 2007

In projected 485‐day studies, Fischer 344 rats and C57BL/6 mice were fed 0.58% butylurea and 0.50% sodium nitrite mixed in the diet separately or in combination. The number and type of neoplasms were not significantly increased in either species receiving butylurea or sodium nitrite only. Feeding the two chemicals simultaneously induced neoplasms of the lung, Zymbal's gland, forestomach, intestine and hemopoietic tissues in rats, and malignant lymphomas in mice. The increased incidence of neoplasms in rats and mice fed butylurea and sodium nitrite in combination may result from in vivo formation of the carcinogen, N‐butyl‐N‐nitrosourea.
Prevention of spontaneous leukemia in mice by oncornavirus immunization
Authors: Fish Donald C. , Bare Robert M. , Hill Paul R. , Huebner Robert J.
Published: February 2007

C57L, NIH, and SWR mice were immunized with inactivated Gross leukemia virus (GLV) and then mated with AKR males. Their F, offspring were then immunized with the murine sarcoma virus pseudotype of GLV, MSV(GLV). The concentrations of infectious ecotropic AKR virus in tail extracts of immunized mice were 100‐to 1,000‐fold lower than in non‐immunized controls when tested at 30–40 days of age. Although viral titers increased slightly with time, the titers remained at least one log10 lower in the immunized mice than in non‐immunized F, control mice at all times tested. The reduction in the level of expression of endogenous ecotropic virus showed a highly significant positive correlation with the reduction in incidence of spontaneous leukemia in these mice. These data thus show that successful immunoprevention of leukemia in mice can be achieved with viral vaccines.
Homogeneously staining regions on marker chromosomes in malignancy
Authors: Kovacs Gy.
Published: February 2007

Direct chromosome analysis with G‐banding revealed homogeneously staining regions (HSR) in five of 16 human solid malignant tumours of different histological types. The HSRs were localized either terminally or interstitially on the marker chromosomes. The great stability of the HSR‐carrying markers in the tumour cells suggests an interrelationship of malignant cell proliferation with the HSR. In a single case the HSR showed a moderate staining intensity for C‐heterochromatin.
Induction of aryl hydrocarbon hydroxylase activity and pulmonary carcinoma
Authors: Gahmberg Carl G. , Sekki Akseli , Kosunen Timo U. , Holsti Lars R. , Mäkelä Olavi
Published: February 2007

Aryl hydrocarbon hydroxylase activity in lymphoblasts from normal Finnish adults and from patients with pulmonary carcinomas and other types of malignancy has been studied by a modification of previously used techniques. High absolute induced aryl hydrocarbon hydroxylase activity was found in 39% of patients with untreated lung cancer but only in 15% of normal people. No increased frequency was found in the control group comprising other malignancies. The diagnosis of pulmonary carcinoma was made at a lower mean age (4.9 years younger) in the individuals with high aryl hydrocarbon hydroxylase activity than in those with low activity. High absolute aryl hydrocarbon hydroxylase activity was dominantly inherited in normal individuals, and the frequency of the Ahb gene in the Finnish population was 8%.
Aryl hydrocarbon hydroxylase inducibility is not altered in bladder cancer patients or their progeny
Authors: Paigen Beverly , Ward Elizabeth , Steenland Kyle , Havens Mary , Sartori Pamela
Published: February 2007

We investigated the possible influence of aryl hydrocarbon hydroxylase (AHH) on susceptibility to bladder cancer in humans. AHH inducibility was measured in the cultured lymphocytes of 16 patients who were being followed after successful treatment for bladder cancer, in 53 progeny of bladder cancer patients, and in matched controls. In both the progeny and patient populations, no evidence was found for a difference between the distribution of AHH inducibility or induced AHH activity compared to the distribution among control individuals. Thus, AHH activity or inducibility does not appear to be a major determinant of bladder cancer risk in humans.
Aryl hydrocarbon hydroxylase inducibility and lymphoblast formation in lung cancer patients
Authors: Prasad R. , Prasad N. , Harrell J. E. , Thornby J. , Liem J. H. , Hudgins P. T. , Tsuang J.
Published: February 2007

Aryl hydrocarbon hydroxylase (AHH) inducibility and lymphoblast formation were studied in lymphocytes from healthy control subjects and from lung cancer patients undergoing radiotherapy. The relationship between AHH inducibility and percentage lymphoblasts was statistically significant only for the pre‐treatment patients (r = 0.598; p<0.05). In the control group and in patients undergoing radiotherapy the correlation between AHH inducibility and lymphoblast formation was positive but statistically it was not significant. Our data do not suggest a linear relationship between AHH inducibility and lymphoblast formation.
Estradiol and progesterone receptors in normal and neoplastic endometrium: Correlations between receptors, histopathological examinations and clinical responses under progestin therapy
Authors: Martin Pierre M. , Rolland Pierre H. , Gammerre Marc , Serment Henri , Toga Maurice
Published: February 2007

Having examined the steroid receptor (SR)' system in normal and neoplastic endometrium from pre‐and postmenopausal women, we investigated the effect of progestin therapy on estrogen and progestin receptors in neoplastic endometrium with respect to histopathological changes and clinical responses of the lesions. In normal endometrium of premenopausal women the estrogen receptor (ER) maximum occurred just before the estradiol (E) peak which is associated with a decrease in ER. In pre‐and postmenopausal women, a high progesterone receptor (PR) value was never associated with a high ER value although in postmenopausal women, PR was only detected when the ER level was high and when there was histological evidence of estrogenic influence. In neoplastic endometrium, a high degree of histological differentiation was associated with simultaneous low ER and high PR values, and vice‐versa. Progestin therapy results in virtually no change either in ER level or in pathological state of the lesions where PR was initially undetectable. In contrast, a positive clinical response was observed in a PR‐positive lesion revealing a differentiated histological type. The effect of P therapy is a fall in both ER and PR to a low level for the former and an undetectable level for the latter. The reasons for PR disappearance involve a nuclear translocation (detected 4 to 8 h after treatment) and a non‐replenishment of PR. Since the clinically responding patients were those with PR and ER positive lesions, the relationship between the presence of PR and a differentiated histological state could reflect the hormonal sensitivity of the tissue. These data also suggest that the effectiveness of P therapy is due to a redifferentiation and to a reduction of the estrogen‐dependent growth of neoplastic endometrial cells.
Characteristics of a low‐molecular‐weight factor extracted from mouse tumors that affects in vitro properties of macrophages
Authors: Cheung Hou T. , Cantarow Walter D. , Sundharadas G.
Published: February 2007

A dialysable low‐molecular‐weight factor capable of affecting in vitro properties of macrophages was extracted from four different mouse tumors. This factor not only modulates closely related properties of peritoneal macrophages such as spreading and migration but also inhibits lipopolysaccharide‐induced tumoricidal activity of these cells. It can be extracted not only from tumor tissues but also from tumor cells grown in vitro. The appearance of this factor is unique to tumors and it is not present in detectable quantities in normal tissues. The factor from one of the tumors, Lewis lung carcinoma, was purified extensively and the partially purified factor retains all the above effects on macrophages. It is not sensitive to pronase or a mixture of bovine spleen phosphodiesterase II, E. coli alkaline phosphatase and pancreatic ribo‐nuclease. The factor is lipid‐like in character and it is soluble in both organic solvents and aqueous media. It has ionizable group(s) and is anionic at neutral pH but non‐ionic under acidic conditions.
Enhancement of tumor outgrowth by tumor‐associated blocking factors
Authors: Hellström K. E. , Hellström I.
Published: February 2007

Transplanted lines of 3‐methylcholanthrene (MCA)‐induced BALB/c sarcomas were used for experiments in which tumors were mechanically suspended in Waymouth's culture medium, the suspensions centrifuged and filtered and the remaining cell‐free “tumor fluids” (TF) tested for activity in vitro and in vivo. TF were found to inhibit (“block”) cell‐mediated cytotoxicity to tumor target cells in vitro with specificity for each tumor tested and even at high dilutions (1:1,000–1:10,000). In vivo, TF enhanced the outgrowth of subcutaneously transplanted tumors in non‐immune syngeneic mice. This enhancement had both specific and non‐specific components, with the non‐specific component being most apparent. Enhancement was best demonstrated when the TF were inoculated together with the tumor inocula. In one of two experiments in which TF were given intraperitoneally, specific enhancement was seen, whereas in the other, inhibition of tumor outgrowth was observed.
Tumor‐associated antigens of chemically‐induced murine tumors; the emergence of MuLV and fetal antigens after serial passage in culture
Authors: Cleveland Patrick H. , Belnap Le Grand P. , Knotts F. Barry , Nayak Shankar K. , Baird Stephen M. , Pilch Yosef H.
Published: February 2007

Using radioiodinated Staphylococcus aureus protein A [125I]SPA to measure syngeneic, allogeneic and heterogeneic IgG bound to murine tumor cells, we performed a serological analysis of surface antigens of 8 solid tumors and 2 leukemias of BALB/c mice (3 chemically‐induced colon carcinomas, 3 chemically‐induced sarcomas, 1 murine leukemia virus (MuLV) induced leukemia, 1 irradiation Induced leukemia, 1 spontaneous melanoma and 1 spontaneous sarcoma). We were able to detect and distinguish between at least five separate antigenic specificities on these tumors. Unique tumor‐associated antigens were found on 3 of the tumors, MuLV related antigens on 8 tumors, fetal antigens on 7 tumors and two distinct common antigens on 7 tumors (common antigen 1 (CA‐1) on 5 tumors and common antigen 2 (CA‐2) on 2 tumors). Neither of the common antigens was found to be sarcoma, carcinoma or tissue‐type specific. A number of tumors which did not originally express either MuLV or fetal antigens in primary cultures expressed these antigens after several serial passages in vitro.
An immunoregulatory factor associated with spleen cells from tumor‐bearing animals.: III. Characterization of the factor's target cells
Authors: Isakov Noah , Hollander Nurit , Segal Shraga , Feldman Michael
Published: February 2007

An immunoregulatory factor associated with spleen cells from tumor‐bearing mice was found to potentiate the generation of antibody‐producing cells (APC). In an attempt to characterize the target cell of this enhancing factor (EF), its activity in mice devoid of mature T lymphocytes was tested. Levels of anti‐SRBC APC were augmented when EF was injected together with SRBC to nude mice and “B” mice. In addition, EF potentiated the antibody response against the IgM‐inducing T. independent pneumococcal polysaccharide SIII antigen. These results suggest that EF most probably exerts its enhancing influence directly on B lymphocytes. In a different line of experiments adoptive secondary responses were performed. Mice were immunized with SRBC as carrier or with the NIP‐chicken erythrocytes (as a source of NIP‐specific primed B cells) in the presence or absence of EF. Various combinations of spleen cells from the donor immunized mice were transferred in a mixture with NIP‐SRBC to lethally irradiated recipient mice. EF did not exert any potentiation effect on helper function, except when primed B cells were used. In contrast, a clear activation or clone expansion of hapten‐specific B cells was observed. These findings indicate that the enhancing factor from tumor‐bearing animals directly affected the anti‐genie triggering of B lymphocytes and their subsequent proliferation and differentiation to antibody‐producing cells.
Tissue CEA in premalignant epithelial lesions and epidermoid carcinoma of the uterine cervix: Prognostic significance
Authors: Lindgren J. , Wahlström T. , Seppälä M.
Published: February 2007

Carcinoembryonic antigen (CEA) was studied by the indirect triple‐bridge immunoperoxidase method in formalin‐fixed paraffin‐embedded tissue specimens from 191 patients with premalignant epithelial lesions or epidermoid carcinoma of the uterine cervix treated 12 years ago. The frequency of tissue CEA positivity was found to increase with advancing clinical disease in the following manner: mild dysplasia, 25%; severe dysplasia, 37%; carcinoma in situ, 60%; invasive carcinoma stage I, 60%; stage lla, 65%; stage Mb, 80%; and stages III and IV, 69%. The prognostic significance of the tissue CEA positivity was studied in two groups of patients formed on the basis of clinical spread and treatment of the disease. The first group of 60 patients with stage I and Ma cancers had undergone radical surgery. The second group of 44 patients with more advanced carcinomas had been treated by radiotherapy alone. No significant difference in the survival rates was observed in either group between patients with CEA‐positive and CEA‐negative tumours. In the light of the absence of CEA from normal cervical epithelium, the increasing occurrence of CEA from premalignant lesions to advancing malignant growth suggests that CEA reflects an aggressive potential in premalignant lesions. However, the survival data on patients with CEA‐positive and ‐negative invasive carcinomas suggest that CEA‐positive cancers are not more malignant than CEA‐negative cancers.
Cancer morbidity and causes of death among danish brewery workers
Authors: Jensen Ole M.
Published: February 2007

Cancer morbidity and causes of death were examined in a retrospective cohort study of 14,313 male members of the Danish Brewery Workers' Union in order to determine health effects of heavy beer drinking, in particular in the aetiology of colorectal cancer. Brewery workers hold the right to consume 6 bottles (2,100 ml) of light pilsener beer (alcohol content 3.7 g1/00 ml) on the premises of the brewery per working day. The cohort included 1,063 mineral‐water factory workers with no free ration of beer. Cancer morbidity and mortality were compared with those of the general population after adjustment for age, sex, area and time trends. Cancer morbidity, 1943–1972, was increased for cancer of the pharynx (RR = 2.09), oesophagus (RR=2.09), liver (RR=1.51) and larynx (RR = 1.98). The risk of these tumours was highest among workers who had had a ration of free beer during 30 or more years of employment. An increased risk of lung cancer (RR‐1.16) corresponds with the risk among persons of low socio‐economic class. These tumour sites accounted for a 9% excess of all malignant neoplasms among members of the BWU. No increased risk for either cancer of the colon (RR = 1.07) or cancer of the rectum (RR = 1.02) was observed. In contrast to studies on “alcoholics”, only deaths from the above‐mentioned cancers, liver cirrhosis (RR=1.77) and motor vehicle accidents (RR = 1.33) were in excess; total mortality was only slightly above expectation (RR = 1.06). The present investigation suggests that the statistical association between beer and colo‐rectal cancer is of a non‐causal nature. It is concluded that the heavy consumption of “weak” alcoholic beverages may increase the risk of upper aero‐digestive tract cancers, and that part of the disease pattern associated with “alcoholism” is unrelated to alcohol consumption.
Non‐random duplication of chromosome 15 in murine T‐cell leukemias induced in mice heterozygous for translocation 1(14:15)6
Authors: Wiener Francis , Spira Jack , Ohno Shinsuke , Haran‐Ghera Nechama , Klein George
Published: February 2007

Trisomy of chromosome 15 is a highly regular feature of murine T‐cell leukemogenesis. We have studied the chromosomal constitution of 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced T‐cell leukemias in C57BL × CBAT6T6 F, mice. The CBAT6T6‐derived chromosome 1(14:15)6 was regularly duplicated whereas the C57BL‐derived normal chromosome 15 was only present in one copy. It was concluded that the gene(s) that tend to duplicate in parallel with the neoplastic transformation of the prothymocyte to an overt leukemie cell have a greater chance of duplicating and/or may have a stronger promoting effect on leukemogenesis if located on the CBA‐derived, structurally rearranged T(14:15)6 than the corresponding genes located on the C57BL‐derived normal chromosome 15.
Neuroendocrine cells in serially passaged rat stomach cancers induced by MNNG
Authors: Kobori O. , Oota K.
Published: February 2007

Five gastric carcinomas, induced in inbred Wistar rats by oral administration of N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG) dissolved in drinking water, were successfully transplanted to isologous rats. The transplants grew to a size of 10 to 35 mm in diameter within 8 to 25 weeks of implantation. In one case, serial transplantations were maintained up to the 11th generation, with occurrence of distant metastasis in the 3rd generation. Histological, histochemical, and electron microscopical comparison of the original and transplanted tumors revealed thet (1) the original tumors were quite well differentiated, forming either papillary or tubular structures, whereas the transplants were more anaplastic and pleomorphic showing often solid nests; and (2) tumor cells with gastrointestinal differentiation and cells with neuroendocrine differentiation were present and evenly distributed in both the original and the serially transplanted tumors. As it is unlikely that the normal and neo‐plastic neuroendocrine cells are growing side‐by‐side with and independently of the epithelial neoplastic components in the present series of transplants, the findings strongly suggest (1) the multidirectional potency of the inbred rat stomach carcinoma cells and (2) the common neoplastic origin of the epithelial and neuroendocrine components.
Preserved foods as possible cancer hazards: Wa rats fed salted fish have mutagenic urine
Authors: Fong L. Y. Y. , Ho J. H. C. , Huang D. P.
Published: February 2007

Six batches of food traditionally and commonly consumed by southern Chinese, including two samples of dried shrimps and four samples of different species of salted fish, were tested for mutagenic properties using Salmonella typhimurium TA98 and TA1000. Mutagenic activities toward both tester strains were found in all preparations. In most cases, these activities were enhanced by liver microsomal activation. Urine collected from experimental rats regularly fed salted fish also showed mutagenic activity. The level of this activity decreased markedly when the experimental rats were transferred from a salted fish diet to Purina rat chow. Our data suggested the presence of mutagenic/carcinogenic substances in some local preserved foods and at least one of them, salted fish, has been suspected on epidemiological and experimental evidence to be a possible co‐carcinogenic factor in the development of nasopharyngeal carcinoma in southern Chinese. Our finding is compatible with this hypothesis.
Enhancement of 2‐acetylaminofluorene liver carcinogenesis in rats fed a choline‐devoid diet
Authors: Lombardi Benito , Shinozuka Hisashi
Published: February 2007

The effects of feeding a choline‐devoid (CD) or a choline‐supplemented (CS) diet on the induction of liver tumors in rats by 2‐acetylaminofluorene (AAF) were investigated. Male Sprague‐Dawley rats were fed either a CD or a CS diet containing 0.0075% AAF. Three to eight animals were killed 1, 3, 4 and 6 months thereafter. Well to moderately well differentiated hepatocellular carcinomas developed in 50% and 75% of rats fed the CD+AAF diet for 4 and 6 months, respectively. Cholangiocarcinomas developed, after 6 months, in 38% of the animals. No tumor developed in rats fed the CS+AAF diet. The results extend to AAF those previously obtained with DL‐ethionine and azaserine showing that feeding a CD diet greatly potentiates the induction in rats of liver tumors by chemical carcinogens.
Hodgkin's disease in patients with previous infectious mononucleosis
Authors: Kvåle Gunnar , Arne Høiby Ernst , Pedersen Einar
Published: February 2007

Patients with a positive reaction to the Paul‐Bunnell test in the period 1961–72 were identified at nine different laboratories in Norway and matched against cases of malignant lymphoma registered at the Cancer Registry of Norway in the period 1961–75. Among 5, 840 patients having a positive Paul‐Bunnell test a total of six developed malignant lymphoma, three of these more than 1 year after the positive Paul‐Bunnell test. The expected number of malignant lymphoma was 2.04. Of the six lymphoma cases, five were classified as Hodgkin's disease (HD). The present investigation agrees well with the findings of other epidemiological studies. There seems to be a small excess in incidence of HD among patients with previous infectious mononucleosis (IM), but both diagnostic problems and possible confounding factors must be taken into account before a possible causal association is considered.
Risk factors for cancer of the testis in young men
Authors: Henderson Brian E. , Benton Barbara , Jing Jennie , Yu Mimi C. , Pike M. C.
Published: February 2007

An individually matched case‐control study of testis cancer in 131 men under age 40 was counducted to investigate antecedent risk factors including events during prenatal life. Ten patients were born with an undescended testis compared to only two controls (p = 0.02), a previously reported risk factor. Two new risk factors were uncovered: six patient‐mothers received hormones during the Index pregnancy compared to only one control‐mother, and eight patient‐mothers and two control‐mothers reported excessive nausea as a complication of the index pregnancy. A hypothesis linking these three factors is presented: viz. that a major risk factor for testis cancer is a relative excess of certain hormones (in particular estrogen) at the time of differentiation of the testes.
Long‐term T‐cell‐mediated immunity to Epstein‐Barr virus in man. III. Activation of cytotoxic T cells in virus‐infected leukocyte cultures
Authors: Moss D. J. , Rickinson A. B. , Pope J. H.
Published: February 2007

Experiments have been conducted to determine the role played by immune T cells in the regression of EB‐virus‐induced transformation which is exclusively seen in leukocyte cultures from seropositive donors. Kinetic studies suggest that, In virus‐infected cultures from such donors, a population of T cells proliferates within the first 2 weeks apparently in response to the appearance of virus‐infected B cells. This proliferation continues to some extent during the period of regression. Nonspecific induction of T‐cell proliferation by PHA did not induce regression in virus‐infected cultures from seronegative donors and actually prevented the regression in seropositive donor cultures. T cells harvested from seropositive donor cultures 11–14 days post infection were generally much more inhibitory to the growth of the autologous EB‐virus‐transformed cell line than were T cells either freshly prepared from whole blood or harvested from corresponding uninfected cultures; this inhibitory activity was either absent or much diminished when assayed against allogeneic target cell lines. The results suggest that virus‐infected individuals possess a pool of virus‐specific memory T cells capable of mounting a cytotoxic response when properly challenged in vitro.
Characterization of normal cervical epithelium, intraepithelial neoplasias and cervical carcinomas in vitro by quantitative studies on nuclear overlap behaviour
Authors: Ebeling K. , Tanneberger St.
Published: February 2007

In an in vitro system the overlap behaviour of cultivated cells of human normal cervical epithelium, dysplasia, carcinoma in situ and invasive cervical carcinoma was examined with a quantitative method initiated by Abercrombie and his co‐workers. The overlap index of cells from normal cervical epithelium was significantly lower than that of all other cells examined (p<0.001), while no significant differences existed between overlap indices of cervical carcinoma cells and ovarian carcinoma cells (p>0.05). Likewise no significant differences were obtained from comparison of overlap indices of cells of carcinoma in situ or dysplasia and cervical carcinoma (p>0.05). The calculated low overlap index of cells cultivated from normal cervical epithelium is a quantitative expression of the monolayering in such cultures. The significant differences of overlap index between cells cultivated from normal cervical epithelium and from intraepithelial atypias and carcinomas of the cervix uteri, and the non‐significant differences between intraepithelial atypias and cervical carcinomas, are considered as an expression of the same biological deviation in preinvasive and invasive lesions of the cervix uteri. Obviously, in spite of the different morphology, dysplasia, carcinoma in situ and invasive carcinoma of the cervix uteri have biologically common features and the different morphological classification of the preinvasive lesions of the cervix uteri does not always reflect their real invasive potential.
Lymphomas resembling lymphoid leukosis in chickens inoculated with reticuloendotheliosis virus
Authors: Witter R. L. , Crittenden L. B.
Published: February 2007

Chickens inoculated as embryos or at hatching with the chick syncytial strain of reticuloendo‐theliosis virus developed a high incidence of lymph‐oid neoplasms between the 17th and 43rd weeks of age, involving principally the liver and bursa of Fabricius. On the basis of organ distribution, latent period, pathology and surface IgM production, the lymphomas closely resembled those of lymphoid leukosis. One inoculated chicken developed a myxosarcoma. No tumors were observed in un‐inoculated controls. The tumor‐bearing chickens were free of infection with Marek's disease virus and exogenous avian leukosis virus (ALV) of subgroups A, B, C or D. However, the chickens were known to express endogenous ALV genes to varying degrees.
Genetic control of in vivo immunity to tumor‐specific transplantation antigens of chemically induced murine fibrosarcomas
Authors: Parmiani Giorgio , Ballinari Dario
Published: February 2007

A possible genetic control of the in vivo immunity to tumor‐specific transplantation antigen (TSTA) of two methylcholanthrene‐induced BALB/c fibro‐sarcomas, C‐1 and ST2, was studied in F1 compatible hosts. Both tumors, which have been previously shown to share their TSTA, lost their immunogenicity in (BALB/c×C3Hf)F1 and C‐1 also in (BALB/c×BALB.K)F1 mice; the immunogenicity of both sarcomas remained unchanged in other hybrid combinations of BALB/c with H‐2b or H‐2a animals. For C‐1 this was true either for a primary immunity to low doses (104 and 5 × 104) of tumor cells or for the secondary immune response measured as a capacity of preimmunized animals to resist a challenge of 105 cells. Since (BALB/c×B10.BR) or (BALB/c×AKR)F1 hybrids (both H‐2d × H‐2k) were able to reject C‐1 cells as strongly as BALB/c mice, the proof of a possible genetic influence involving dominant genes coding for low responsiveness to C‐1 or to ST2 and linked to H‐2k haplotype was sought in a back‐cross experiment. The primary and secondary immune response to C‐1 and the secondary immunity to ST2 were evaluated in BALB/c × (BALB/c × C3Hf) back‐cross mice. Results for both tumors were compatible with the presence of an H‐2 dominant gene (or cluster of genes), whose products suppress immunity to TSTA; the linkage of low anti‐tumor responsiveness with H‐2k was demonstrated for both C‐1 and ST2. Further evidence for this linkage was found in the study of immunity to C‐1 in (BALB/c×C3Hf)×(BALB/c×C3Hf) F2 animals. An attempt to map gene(s) governing the low immune response to C‐1 and ST2 was performed by studying the anti‐tumor immunity of BALB/c, (BALB/c×A), (BALB/c×A.TL), (BALB/c×A.AL), (BALB/c×B10.A), [BALB/c×B10.A(4R) and (BALB/c×C3H.OH]F1 mice. It was found that Kk and Dk regions are not necessary for the low immunity to C‐1 to be expressed, therefore mapping the relevant gene(s) in the Ik region. The low immune response of (BALB/c×C3H.OH)F1 mice to C‐1, however, suggested that Dk genes are also important in this phenomenon. For ST2, only BALB/c×C3H.OH animals showed a low anti‐tumor response thus mapping genes coding for a suppression of anti‐ST2 immunity in the Dk region. Since (BALB/c×B10.A) but not (BALB/c × A)F1 mice (both hybrids having an identical H‐2d × H‐2a genotype but different non‐H‐2 backgrounds) were able to develop an anti‐C‐1 immunity, an effect of non‐H‐2 factors which may counteract the suppressive activity of MHC genes is implied. The possible mechanims of this genetic control are discussed.
Transplanted cultured cells from pregnancy‐dependent mammary tumors have a heterogenous developmental potential
Authors: Aidells Bruce D. , Lee Audrey E.
Published: February 2007

Cultured cells derived from pregnancy‐dependent mouse mammary tumors (plaques) when transplanted into the gland‐free mammary fat pad display a heterogeneous developmental potential. They not only gave rise to plaques but also produced normal mammary gland, hyperplastic alvoelar nodules (HAN), and autonomous mammary tumors.
Natural cell‐mediated cytotoxicity in hamsters
Authors: Datta Surjit K. , Gallagher Michael T. , Trentin John J.
Published: February 2007

Lymphoid cells from normal inbred LSH and random‐bred Syrian golden hamsters were evaluated for natural cytotoxic activity against cultured simian adenovirus 7 (SAT)‐induced lymphoma of the LSH hamster employing the 51Cr‐release cytotoxlcity assay. Natural cytotoxic reactivity was found in both inbred and random‐bred hamsters. The level of activity was much higher in random‐bred (38.2% lysis) than in inbred (14.9%) hamsters. The percentage lysis of SA7 target cells was proportional to the effector:target cell (E:T) ratio. Natural cytotoxic reactivity was high in both spleen and bone marrow intermediate in mesenteric lymph node, and low or non‐existent in thymus. Natural cytotoxic responses were present In 4‐to 7‐day‐old, adult and aged (1‐to 11/2‐year‐old) hamsters. Exposure of hamsters to 1,100 R of whole‐body irradiation had little or no effect on natural cytotoxic reactivity, indicating the radio‐resistant nature of the reactivity in hamsters, as in mice. Treatment of hamsters with a single dose of either 500 mg cytoxan/kg intraperitoneally (IP), or 5 mg carrageenan IP markedly suppressed their natural cytotoxic responses, as in mice. Growth of transplanted SA7 tumor in inbred hamsters or of D., lymphoma in random‐bred hamsters strongly inhibited the natural spleen‐cell‐mediated lysis of SA7 lymphoma cells. Thus, while hamster natural cytotoxic activity shared most of the properties of mouse NK activity, it differed in (1) appearing earlier in life (2) increasing progressively into older age (1 1/2 years) and (3) being as high in bone marrow as in spleen, or higher.
Simultaneous presence of EBNA‐positive and colony‐forming cells in peripheral blood of patients with infectious mononucleosis
Authors: Katsuki T. , Hinuma Y. , Saito T. , Yamamoto J. , Hirashima Y. , Sudoh H. , Deguchi M. , Motokawa M.
Published: February 2007

EBNA‐positive lymphoblast cells were detected in 0.1 to 0.9% of the T‐cell‐depleted lymphocytes obtained from peripheral blood samples of five patients with infectious mononucleosis (IM). The same blood specimens from four of the five patients contained cells that formed EBNA‐positive colonies in soft agar containing EBV antibodies. The ratio of the colony formers to EBNA‐positive cells was higher in blood samples taken early in the disease than in those obtained in later stages of the disease. The present results strongly suggest that EBV‐transformed cells are present in the peripheral circulation of IM patients and that such cells can directly give rise to immortalized cetl lines in vitro.
Liver‐colonizing melanoma cells selected from B‐16 melanoma
Authors: Tao Tien‐Wen , Matter Alex , Vogel Kurt , Burger Max M.
Published: February 2007

Liver‐colonizing tumor cells were selected from B‐16 melanoma by a stepwise procedure: (1) injection of the original cells through the portal circulation; (2) removal of tumor cells from the hepatic tumor nodules for culture in vitro; (3) reinjection of such cells through the portal circulation and repetition of steps 2 and 3 eight times. The predilection of these selected cells to form tumors in the liver was clearly demonstrated following injection of the cells intra‐arterially. The accuracy of the injection technique was controlled by monitoring amounts of injected radioactively labelled Sephadex microspheres. This liver‐colonizing preference was not exclusive, but relative.
Cell‐mediated cytotoxicity for cultured autologous melanoma cells
Authors: Livingston P. O. , Shiku H. , Bean M. A. , Pinsky C. M. , Oettgen H. F. , Old L. J.
Published: February 2007

Peripheral blood lymphocytes from 32 patients with malignant melanoma were tested for cell‐mediated cytotoxicity (CMC) against cultured autologous melanoma cells. Effector cells were prepared from venous blood by defibrination, gel sedimentation, nylon column filtration, and lysis of remaining erythrocytes with NH4Cl. Melanoma cells prelabelled with [3H]proline were used as target cells in a 40‐h assay and CMC was evaluated against standards obtained with blood lymphocytes from the least reactive normal donor. Reproducible autologous CMC was detected in 18 of 32 patients in a series of 367 total tests. CMC correlated with tumor volume (5–500 cm3) but not with tumor stage or DNCB reactivity. Preliminary results indicated that autologous CMC was not affected by treatment with DTIC, dexamethasone, intralesional BCG, radiation therapy, or partial surgical excision. Lack of consistent CMC in 14 patients could not be attributed to a measurable decrease in general immune capacity or to increased resistance of the patients' melanoma cells to CMC in general. Fibro‐blasts were more resistant to CMC than melanoma cells, and therefore of questionable value for defining specificity in direct tests.
Selective cytotoxicity of tunicamycin for transformed cells
Authors: Olden Kenneth , Pratt Robert M. , Yamada Kenneth M.
Published: February 2007

We have studied the effects of tunicamycin, an inhibitor of dolichol pyrophosphate‐dependent glycosylation of proteins, on the viability of transformed and non‐transformed fibroblasts in culture. We have shown that a low concentration of tunicamycin (0.05 μg/ml or 5 × 10−8 M) is cytotoxic toward a variety of transformed cell lines, including virally or chemically transformed fibroblasts from chick embryo, rat kidney, human lung, and mouse. The corresponding non‐transformed cell lines were resistant to the same and a 10‐fold higher concentration of tunicamycin. However, transformed permanent cell lines were also found to be resistant to tunicamycin. The relationship between transformation and tunicamycin cytotoxicity was strengthened by the finding that chick embryo fibroblasts infected by the temperature‐sensitive viral mutants ts68 or T5 are killed by the drug only at the temperature at which transformation is expressed. The LD50 for sensitive transformed cell lines ranged from 0.02 to 0.034 μ/ml tunicamycin. Maximal cytotoxic effects to transformed cells were produced at tunicamycin concentrations which only slightly inhibited protein synthesis in non‐transformed cells (17–22% in 24 h). There was a good correlation between the susceptibility of transformed cells to tunicamycin cytotoxicity and their sensitivity to tunicamycin inhibition of protein glycosylation, 2‐deoxy‐D‐glucose transport, and glucose metabolism. These results indicate that tunicamycin interferes with some cellular process critical for the survival of many transformed cells but not of non‐transformed cells. We speculate that the cytotoxicity of this drug towards transformed cells may result from impaired rates of nutrient transport, although other mechanisms are possible. Tunicamycin may, therefore, be therapeutically useful as an anti‐tumor agent to selectively kill certain types of malignant cells, while sparing non‐transformed cells.
Inhibition of mammary tumorigenesis in GR mice with 2‐bromo‐α‐ergocryptine
Authors: Welsch Clifford W. , Goodrich‐Smith Margaret , Brown Carolyn K. , Wilson Mark
Published: February 2007

A high incidence of mammary tumors is found in multiparous GR mice during the 2nd and 3rd pregnancies and in nulliparous GR mice treated with estrone/progesterone. The purpose of this study was to determine if prolactin is a contributing hormone in the genesis of these neoplasms. In one series of experiments, 238 15‐week‐old nulliparous GR mice were treated with estrone (drinking water, 0.5 mg/liter) plus progesterone (30 mg progesterone pellet with cholesterol, implanted SC once monthly) for a period of 13 weeks. Half of these mice were injected SC once daily with 100 μg of the prolactin‐suppressing drug 2‐bromo‐α‐ergocryptine (CB‐154) for the duration of hormone treatment, and the other half were injected SC once daily with 0.9% NaCl solution (controls). In another series of experiments, 87 pregnant GR mice were divided into two groups and injected SC once daily from day 7 to 21 of pregnancy with 0.9% NaCl solution (controls) or CB‐154 (100 μg/mouse). In the first series, the numbers of mice with mammary tumors and total number of mammary tumors were: controls, 58/119 (49%) and 73; CB‐154 treatment, 34/119 (29%) and 37, respectively. In the second series, the numbers were: controls, 39/44 (89%) and 73; CB‐154 treatment, 24/43 (56%) and 43, respectively. In both studies, CB‐154 treatment significantly (p<0.05–0.005) reduced the percentage of mice with mammary tumors and total number of mammary tumors. These results provide evidence that prolactin is a contributing hormone in the genesis of estrone/progesterone and pregnancy‐induced mammary tumors in female GR mice.