1) Intracutaneous injection of lipopolysaccharide of Proteus vulgaris into ddY or DDD mice after inoculation of Ehrlich tumor cells which had been sensitized with rabbit antiserum altered both the survival rate and resistance of the mice to growth of the tumor. The survival rate and the resistance were enhanced by lipopolysaccharide treatment when the tumor cells had been sensitized with diluted antiserum but were reduced when the tumor cells had been sensitized with undiluted antiserum.
2) Reticuloendothelial activity, estimated by measuring the clearance of colloidal ¹⁹⁸Au from the blood, increased about 2 fold after treatment with lipopolysaccharide.
3) Sera of resistant mice obtained 30 days after the initial induction showed suppressive activity against transplantation of the tumor. This activity was increased by treatment with lipopolysaccharide after inoculation of sensitized tumor cells. These sera did not show any cytotoxic activity against tumor cells in vitro.
4) A larger amount of α- and β-globulin fractions was found in sera of resistant mice than in normal serum by polyacrylamide gel electrophoresis.

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This paper describes the isolation of an agent, capable of eliciting erythroblastosis in both rats and mice, in the course of cell-free transmission experiment in the preceding study. All of four litters of W/Fu rats developed a marked splenomegaly with severe anemia 35-41 days after neonatal inoculation of leukemic cell-free supernatant prepared from a W/Fu rat with thymic lymphoma, which was originally derived from thymic lymphoma in C57BL/Ka mouse treated with N-nitrosobutylurea. The proliferating cells in the spleen and liver were identified as the immature erythroblasts. The inoculation of spleen cells from the W/Fu rat with erthroblastosis into syngeneic suckling rats resulted in fatal erythroblastosis within 3 weeks. In ACI rats, erythroblastosis could be transplanted even into young adult syngeneic recipients within 1 month. All strains of rats and mice thus far tested were susceptible to viral induction of erythroblastosis with a short latent period. It was found that anti-erythroblastosis serum distinctly reacted with spleen cells of W/Fu rats with erythroblastosis. High cytotoxic activity of anti-Gross serum was also found in every case of erythroblastosis. Furthermore, high cytotoxic activity of anti-erythroblastosis serum remained after absorption with Gross tumor. Infectivity of erythroblastosis virus in rats could be neutralized by incubating in vitro with anti-Gross serum produced in syngeneic rats. Many mature C-type virus particles were observed in intercellular spaces by electron microscopy. The erythroblastosis virus was inactivated by heat (56° for 30min) or ether. The virus was sedimented by centrifugation at 40, 000rpm for 110min.

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An analytical study was made on the Yoshida ascites sarcoma cell population as regards the producibility of α-fetoprotein. Results were suggestive of the presence of α-fetoprotein-producing cells within the tumor cell population and their variable producibility of α-fetoprotein.

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The humoral inhibitor, which may act as an essential part in the regulatory mechanism of cell division in the regenerating rat liver, was investigated by measuring the concentration of protein components in the partially hepatectomized rat plasma after the operation and by testing the mitosis-delaying effect of the plasma protein components on the regenerating rat liver.
The concentration of α₁-globulin in the partially hepatectomized rat plasma fell sharply to about one-third of that of normal non-hepatectomized rats 18hr after the operation, 12hr before the peak of mitosis and, thereafter, rose steadily to the highest value at 168hr after the operation, when the liver regained 90% of the preoperative weight and mitosis almost ended. The time-course changes in the concentration of other protein components were too slow and too small to account for the rapid onset of mitosis. Only α₁-globulin seems to satisfy the first necessary condition that a humoral inhibitor should satisfy.
The experiments by intraperitoneal injection of plasma protein components into partially hepatectomized rats have suggested that the mitosis-delaying effect may be present in α₁-globulin and β-globulin fractions, but absent in albumin fraction, and it may be lost by heating at 65° for 30min. Both α₁-globulin fraction, which is a high molecular fraction by gel filtration, and β-globulin fraction seem to satisfy the second necessary condition that a humoral inhibitor should satisfy; α₁-globulin fraction seems to satisfy two necessary conditions, while β-globulin fraction does only one of the two.
These results suggest that the humoral inhibitor or hepatocyte-specific mitotic inhibitor may be present in α1-globulin fraction and may be a heat-labile, high molecular entity.

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The effect of various factors on the development of urinary bladder tumor in rats, guinea pigs, and hamsters given N-butyl-N-(4-hydroxybutyl)nitrosoamine was examined histologically. The effect of sex and age, and of the dose and period of administration of N-butyl-N-(4-hydroxybutyl)nitrosoamine on the incidence of urinary bladder tumors in rats was also investigated.
No sex difference was found in the incidence of urinary bladder cancer in rats. However, the incidence of cancer and of squamous metaplasia in areas of cancerous tissues was greatly influenced by the age of animals, being much higher in older rats than in younger rats.
For development of urinary bladder cancer in rats, the minimum carcinogenic dose of N-butyl-N-(4-hydroxybutyl)nitrosoamine given in the drinking water is 0.005% while 0.001% is the maximum non-carcinogenic dose. On administration of 0.1% carcinogen solution to rats, the minimum period for the induction of urinary bladder cancer is 4 weeks.
Guinea pigs and hamsters were less susceptible than Wistar strain rats to the induction of urinary bladder cancer by N-butyl-N-(4-hydroxybutyl)nitrosoamine.

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Young adult (AKR×SL)F₁ hybrid mice were thymectomized and transplanted subcutaneously with thymus tissue from AKR, SL, or F₁ hybrid mice of the same age. Only thymus grafts from AKR could restore the susceptibility of thymectomized mice to lymphoma development, those from SL and F₁ hybrids being ineffective. Grossly most lymphomas developing in thymectomized mice with thymus grafts were not accompanied by the enlargement of thymus grafts, and histologically belonged to the reticulum cell sarcomas. Influence of thymus grafts on the lymphoma development was suggested to be due to the interaction of two different mechanisms, viral and immunological.

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Two cases of epidermodysplasia verruciformis (EV), a human precancerous condition, were studied by light and electron microscopy. Skin lesions were histologically typical of EV. Virus particles were observed in all of five typical benign lesions tested. They were observed in the nucleus of cells in the upper epidermal layers. Negative staining of tissue extracts revealed that virus particles were 50-60nm in diameter and had the same surface structure as the virus of human common warts, with 72 capsomeres arranged in the right-handed form. A lesion on the upper thigh of one of the two cases showed a histology of early squamous cell carcinoma. In this case its transition from the typical benign lesion was evident. A few virus particles were also observed in the negatively stained tissue extract of this lesion showing the histology of early squamous cell carcinoma. These results suggest that the skin lesions of EV induced by a virus identical with or related to the wart virus become malignant and that the sunlight is not essential though it accelerates the malignant transformation of the skin lesions of EV. A comparative scheme on the tumorigenic process in EV and common warts was proposed and discussed.

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The T antigen was stained successfully by immuno-electron microscopic method applied directly on the ultrathin section of SV40-transformed kidney cells of an African green monkey embedded in water-soluble plastics (glycol methacrylate). The results showed that the T-antigen was associated closely with the nuclear chromatin.

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After subcutaneous injection of 4-nitroquinoline 1-oxide, drastic changes in fine structure are observed in the Clara cells in the terminal bronchiole of the A strain suckling mouse. In contrast to the Clara cells, no changes are seen in the ciliated cells within 16hr.

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Effects of 4-nitroquinoline 1-oxide on chromosomes of cultured human lymphocytes were studied. Both chromatid and chromosome type aberrations were detected. These results and its relation to marker chromosomes found in malignant cells transformed by 4-nitroquinoline 1-oxide were discussed.

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In both thigh and footpad inoculations of mouse leukemia L-1210 cells, better chemotherapeutic effect was found in the latter inoculation system. Together with this result and bioassay of lymph nodes in both systems, thigh inoculation was considered to be a more appropriate model for chemotherapy of lymph node metastasis.

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Multicarcinogenicity of N-nitrosobutylurea can be disclosed by disrupting the physiological equilibrium of a particular cell population. This was demonstrated in the induction of leukemia, mammary tumors, lung adenomas, and hepatomas in variously conditioned mice and rats.

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In the process of chemical leukemogenesis of the mouse, thymus cell susceptibility to anti-θ C3H serum was markedly reduced in the preleukemic stage by the depletion of small lymphocytes from the thymic cortex. Correlation between types of leukemias and the θ-antigen was discussed.

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The molecule of carcinoembryonic antigen seemed to be composed of two antigenic moieties; one is specific for cancerous tissues in digestive organs and the other is identical to an antigen which was found to be extractable from feces of normal adults in fairly large quantities.

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A linear relationship was found between the concentration of Vincristine and the percentage of arrested metaphase in Yoshida sarcoma cells treated with this drug. This finding was utilized as a bioassay method for Vincristine.

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