The influence of oral administration of lithocholic acid on the development of liver tumors induced by DL-ethionine was studied. It was found that oral administration of lithocholic acid did not induce neoplasia in rat liver but it clearly promoted the development of hyperplastic nodules and hepatomas in rat liver induced by DL-ethionine. The hyperplastic nodules induced by DL-ethionine plus lithocholic acid were larger and more numerous than those induced by DL-ethionine alone. Rats receiving a diet containing 0.5% lithocholic acid without DL-ethionine showed marked fibrotic changes in the liver.
Under the electron microscope, annulate lamellae were seen in the cytoplasm of many cells of hyperplastic nodules in the liver induced by a diet containing DL-ethionine plus lithocholic acid.

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A mixed type colony in the spleen in myelomonocytic leukemia of RFM/Un strain of mice, using the endocolonizationte chnique, is reported. This consists of myeloid leukemia cells and normoblasts in approximately eqaul proportions. The neoplastic nature of myeloid and erythroid components in this colony type and uni- or multipotentiality of stem cells are discussed.

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Mechanism of the rejection of Friend virus-infected tumor cells in the host was analyzed from the relationship between the positive rate of immunofluorescent viral or surface antigens and the growth rate of Friend virus-infected tumor cells in the host. The rate of both viral and surface antigens was generally inversely correlated with the growth of the Friend virus-infected tumors. The minimum fluorescence-positive rate required to produce regression of the tumor infected with Friend virus deviated from 35.6 to 70.0% in viral antigens and from 0.06 to 0.34 as fluorescence index in surface antigens. Variation in fluorescence-positive rate depending on the tumor lines used may be due to the difference in the grade of antigenicity of the tumor. The mechanism of the regression of Friend virus-infected tumors was discussed.

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After a long-term observation of the local application of 7, 12-dimethylbenz[a]-anthracene (DMBA) to the mucosa of the glandular stomach of rats, 11 of 46 rats exhibited carcinoma at the site of application of the carcinogen. Microscopically 9 were adenocarcinoma and 2, anaplastic growth patterns consisting of epithelial-like cells originating either in glandular epithelium or in non-epithelial cells. Two of the animals with carcinoma had hemorrhagic ascites containing tumor cells. One of these showed an ascites tumor in a pure culture state of tumor cells.
Autoradiographic study using ³H-thymidine revealed that the regenerating epithelium at the margin of the ulcer, which was induced by DMBA treatment, showed the highest DNA synthesis and that the heterotopic epithelium without cytological atypism almost failed to synthesize DNA.
Transplantation of 6 nodules induced by DMBA was attempted and one carcinoma was successfully transplanted up to the second generation.

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Bleomycina, new antitumor antibiotic with a proved activity againsts quamous cell carcinomas and malignant lymphomas, was found to possess very little immunosuppressive effect. Its dose of 50mg/kg (LD₁₀) or 75mg/kg (LD₂₀) did not suppress the formation of circulating antibody in mice immunized with sheep blood cells. Hemolytic plaque-forming cells in spleens of these mice were minimally suppressed by the above doses of Bleomycin but the degree of suppression was quite low compared to the suppressive effect of Daunomycin in 19mg/kg (LD₁₀). The possible explanations for this lack of immunosuppressive effect in mice studied are a low concentration of the antibiotic in spleen and other lymphoid organs and its ready inactivation in these tissues.

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Peritoneal lymphocytic cells obtained from Donryu rats which had been immunized against Yoshida sarcoma cells showed a remarkable cytotoxic effect on tumor cells in vitro. Cytotoxic activity of the lymphocytic cells was enhanced after their incubation for 24-72hr with or without Yoshida sarcoma cells, although the number of cultured lymphocytic cells decreased to one-third to one-fifth and percentage of lymphocytic cells capable of adhering to tumor cells decreased to one-half of the initial count. Continous observation of destructive process of a Yoshida sarcoma cell by adhesion of lymphocytic cells revealed that one precultured lymphocytic cell was able to destroy one tumor cell, although two or more adhering lymphocytic cells were required to destroy one tumor cell unless the lymphocytic cells had been cultured. The fact that cytotoxic activity of some population of immune lymphocytic cells is enhanced after in vitro culture indicates that a part of the mechanism of cell-mediated immune reaction in the present system is associated with a dynamic function of effector lymphocytic cells such as the production of a cytotoxic factor. However, no cytotoxic factor was demonstrable either from the medium in which immune lymphocytic cells were cultured with or without antigenic tumor cells or from the homogenate of cultured lymphocytic cells.

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Mouse liver was found to contain two kinds of pyruvate kinase; one neutralizable and the other not neutralizable by anti-rat muscle pyruvate kinase serum. The former was named tentatively muscle type and the latter liver type. Mouse muscle pyruvate kinase was neutralized almost completely by the anti-rat muscle pyruvate kinase serum.
About 90% of pyruvate kinase from Ehrlich ascites cells was also neutralized by the antiserum, and electrofocusing profile of this enzyme was similar to that of muscle enzyme.
Muscle-type activities of aldolase and pyruvate kinase in mouse liver increased both by inoculation of Ehrlich ascites tumor cells and by administration of a hepatocarcinogen, N, N'-2, 7-fluorenylenebisacetamide. Electrofocusing profile revealed that the increased muscle-type pyruvate kinase was a mixture of several enzyme species, one of them having an isoelectric point consistent with the muscle pyruvate kinase, and others with an isoelectric point intermediate between those of liver-type and muscle-type pyruvate kinases.

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A stimulative effect of immunosuppressor, azathiopurine, on the development of 3-methylcholanthrene-induced skin tumor of mice and on that of solid type of Ehrlich carcinoma was examined. The dose of azathiopurine, 0.5, 2.0, or 8.0mg/kg/day for 7 days or twice a week for 15 weeks did not affect the regression of both kinds of tumor. Mice treated with azathiopurine (40mg/kg/day for 5 days) prior to the subcutaneous transplantation of Ehrlich carcinoma and after the transplantation (0.5mg/kg/day for 7 days) showed a progressive development of tumor weight in 14 days by 185% compared to the control without the treatment.
Prior to the painting of 3-methylcholanthrene on the skin of a mouse, azathiopurine (40mg/kg) was given for 5 days. After 2 days of interval without the treatment mice were given 3-methylcholanthrene and azathiopurine (8 and 2mg/kg) twice a week for 15 weeks. Microscopic examinations showed a progressive development of malignant tumor in the group given azathiopurine plus 3-methylcholanthrene (incidence, 39%), compared to that given 3-methylcholanthrene alone (18%).
The immunosuppressive state induced by azathiopurine in mice was studied for the activity of reticuloendothelial system as observed by the clearance of ¹⁹⁸Au from the blood.

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Chromosomes were studied in blood and marrow cells of 10 patients with acute myelogenous leukemia, under several different observational conditions, i.e., in direct preparations and in cultures with and without phytohemagglutinin.
Abnormal karyotypes were observed in 5 cases; 2 cases with a presumptive C/G translocation, 1 case showing a Ph¹-like chromosome, 1 hyperdiploid case having 52 chromosomes, and 1 case characterized by a ring chromosome. The remaining 5 cases showed a normal karyotype.
Although direct marrow preparations were of potential value for cytogenetic analysis of leukemic cells, blood and marrow cultures without phytohemagglutinin were also useful for detection of abnormal karyotypes undetectable by the direct method as well as for the evaluation of chromosomally normal leukemic cells.

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Iodine which is known to produce cation radical of 3, 4-benzopyrene was injected immediately after a single subcutaneous injection of 3, 4-benzoypyrene. No accelerating effect on the carcinogenicity of 3, 4-benzopyrene was observed in both experiments using tricaprylin and benzene as a solvent, though the tumor incidence in the former solvent was far higher than that in the latter solvent. This result does not lend support to the proposition that the cation radical of 3, 4-benzopyrene is a proximate form of 3, 4-benzopyrene.

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L-strain cells were treated with cigarette tar for 3hr. The cells treated with 25 (LT-25) or 100 (LT-100) μg/ml of tar showed enlarged and vacuolated cytoplasms, and giant cells were found immediately after the treatment. Cells treated with 250 or 500μg/ml of tar died with in 24hr after the treatment. Cells of LT-100 and LT-25 showed a remarkable growth 50 or 60 days after the treatment as compared with control cells. Plating efficiency was also different in treated and nontreated cells. About 70 days after the treatment, 10⁵ to 10⁶ cells from the treated and control cells were injected into the newborn C3H mice. Tumor formation was observed in animals injected with LT-100 and LT-25 cells, but not in animals inoculated with LA-100 (ethanol-treated cells), or non-treated cells except in only one case. Some numerical changes in chromosome number were observed but no cytomorphological changes occurred in the treated cells.

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Repeated subcutaneous injections of N, N'-dimethylnitrosourea into Syrian hamsters induced malignant tumours in the forestomach, breast, uterus, liver, and pancreas. From the above observations, the degree of methylation of cellular components in a particular organ of the animal or a subsequent derivative of this compound may play a major rôle.

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Malignant tumors were induced in 9 of 18 mice treated with 3-methyl-4-nitropyridine 1-oxide, a pyridine series of derivatives analogous to carcinogenic 4-nitroquinoline 1-oxide.

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Exocrine tumors of the pancreas were produced in Sprague-Dawley rats following a single intravenous injection of 4-hydroxyaminoquinoline 1-oxide in dose levels of 6, 9, and 13mg/kg, There was neither local invasion, spread to the mesentery, nor distant metastasis.

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