Effect of hydrocortisone, glucagon, dibutyryl cyclic-AMP, and theophylline on tyrosine aminotransferase activity of tumors and the host liver was studied in Donryu rats bearing Yoshida sarcoma and its variant lines, LY-52, LY-54, and LY-80, and Yoshida ascites hepatoma AH-109A under controlled lighting condition. The enzyme activities in LY-52, LY-54, LY-80, and AH-109A tumors were modified by the ratio of tumor size to the body weight of rats bearing the tumor, and relatively higher activity was measured in the rat bearing smaller sized tumor. Increase in the enzyme activity by simultaneous treatment with hydrocortisone and glucagon was observed in Yoshida sarcoma. Further, increased activity by the administration of theophylline in LY-54 cells and by the repeated injection of hydrocortisone in LY-80 cells was also determined. It is of interest to note that the enzyme activity, even in the increased levels after the hormonal treatment, in each tumor line reported herein is apparently lower than that in normal adult rat liver and in the liver from tumor-bearing rat, and various responses to hormonal treatments between the parent Yoshida sarcoma and its variant lines are observed, as shown by different responses between the liver in rats bearing tumor and normal rat liver. Process of change in the enzyme regulation of the tumor during transformation from Yoshida sarcoma to its variant lines was discussed briefly.

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Antitumor activity of cyclophosphamide and Mitomycin-C was enhanced by centrophenoxine. ED₉₀ of cyclophosphamide in ascites sarcoma-180 was lowered from 46 to 15mg/kg/day by the combination with 300mg/kg/day of centrophenoxine, and therapeutic index was also increased from 9.6 to 18.6 or 16.3. However, the activity of other antitumor agents tested was not enhanced. Enhancing effect of centrophenoxine was also found in various other tumors such as Ehrlich ascites carcinoma, Nakahara-Fukuoka sarcoma, and adenocarcinoma-755. p-Chlorophenoxyacetic acid as a partial structure of centrophenoxine seemed to be the proximate potentiator for cyclophosphamide but was toxic. This toxicity was reduced when combined with dimethylaminoethanol.

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Skin-muscle cells of golden hamster embryos were transformed in vitro by bovine adenovirus type-3. Transformed foci appeared 32 to 65 days after infection. By backtransplantation of the transformed cells, tumors developed in hamsters, which resembled histologically the primary tumor induced by the virus. While the virus was not isolated from the transformed cells, the virus-specific T-antigen was demonstrated.

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Studies were made on the ultrastructure of the nuclei in cells of hepatic cell carcinomas and hyperplastic nodules induced by carcinogens, DL-ethionine, 2-fluorenylacetamide, and 3'-methyl-4-(dimethylamino)azobenzene. The cells of hepatic cell carcinomas were divided into the following 3 types according to their nuclear structure: Cells with a structure similar to that of hyperplastic nodular cells, cells with an intermediate structure, and cells with the typical characteristics of cancer cells. Cells having a nuclear structure similar to that of nodular cells seemed to be transformed from nodular cells to hepatic carcinoma cells. The latter contained small condensed chromatin particles on the inner layer of the nuclear envelope (perinuclear chromatin) and in the peripheral part of the nucleolus (nucleolus-associated chromatin), in contrast to nodular cell nuclei in which all the chromatin fibrils were loose and dispersed in the nucleoplasm. Another difference was that they had round nucleoli with nucleolonemas of reticular form, in contrast to nodular cells in which the nucleolonemas showed remarkable deformity and contained many granular components.
This indicates that the process of transformation from nodular cells to cells of hepatic cell carcinomas is equivalent to regeneration.

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Comparative examinations were made on the intermolecular interaction between DNA and quinolines, 4, 6-dinitroquinoline 1-oxide, 6-chloro-4-nitroquinoline 1-oxide, 4-nitroquinoline 1-oxide, 2-methyl-4-nitroquinoline 1-oxide, 4-nitroquinoline, and quinoline 1-oxide. Quantitative analyses were made on the visible difference spectra which were produced by the interaction of the quinolines with DNA and deoxyribonucleosides. It was concluded that a π-π charge transfer between quinolines and the base moiety of the macromolecule played an important rôle in the interaction between DNA and the quinolines. With the exception of the 4, 6-dinitro derivative having a powerful antitumor activity, there was a parallelism between the extent of charge transfer between quinolines and DNA, and carcinogenic activity of the quinolines.

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In 2 out of 3 patients who underwent surgery for thyroid adenocarcinoma but later died of other causes, many microscopic metastases were found in the lungs by careful autopsy examinations. No visible cancer foci were grossly detected in the lungs at autopsy. These 2 patients with metastasis in the lungs had no clinical symptoms or laboratory findings suggesting metastasis. The mitotic index of thyroid papillary and follicular adenocarcinoma was much less than that of other cancers. It is suggested that favorable prognosis of thyroid adenocarcinoma, despite its high incidence of metastasis, is related to its extremely slow proliferation rate.

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Serial passages of murine sarcoma virus (Moloney) (MSV-M) have been maintained by cell-free transmission of mouse tumors through BALB/c newborn mice (MSV-M stock line) and by cell transplants of an MSV-induced sarcoma through young BALB/c mice (MSV-sarcoma line). A consecutive cell-free passage through newborn WKA rats has also been established from the rat tumors induced by cellfree filtrate of the latter sarcoma (MSV-rat line).
Biological activity of the MSV, and the result of macroscopic, histological, and ultrastructural examinations of the lesions induced in WKA rats and BALB/c mice were compared among three passage lines. Supplementary experiments were made with different strains of mice and rats. Results showed that a neoplastic response of target cells to the viral infection differed between two species of the animals. In general, all lines of viruses were oncogenic to both mice and rats but produced predominantly a myosarcoma in mice whereas osteosarcoma was produced in rats. However, development of myosarcoma in association with bone tumor was sometimes noted in rats receiving mouse-derived virus. Lymphoma was found to be a rare occurrence in both animals when they survived for longer periods. Occurrence of bone tissue hyperplasia adjacent to neoplastic lesions became frequent in mice with increased passages of virus or with rat-derived virus. In rats, on the other hand, cystic lesions of lymph nodes were found in high incidence. Rats were found to be less sensitive to the MSV infection than mice; in rats, tumor induction required doses of the inocula 10⁴ times higher than that in mice. Tumor incidence with mousederived MSV increased with the increase of passage whereas that with rat-derived MSV showed little increase. The type-C virus particles were observed in tumor cells, splenic cells, and megakaryocytes from spleen and bone marrow of both species of animals. These findings suggest the possible derivation of a varied MSV-M which acquired bone tumor inducing ability. Rat tumors were transplantable in suckling and young rats. However, a high rate of tumor regression occurred.

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A cell line was established in culture from an osteosarcoma induced in a Wistar-King-Aptekman (WKA) rat by Moloney's isolate of murine sarcoma virus (MSV-M). In early passages this line showed morphologically a non-malignant fibroblastic growth forming a thin monolayer but released MSV-M of low infectivity. Thus it appeared to be an MSV-persistent cell line (RMS-1N). After the 7th culture passage (about 5.5 months later), however, some fractions of these cells underwent morphological alterations into refractile fusiform cells, and subsequently transformed into small rounded cells. Two clonal lines of the transformed cells (RMS-1F1 and 2) were derived from the RMS-1N cells and another one (RMS-1F3) was from the same line after about 18 months of cultivations. Additional clones (RMS-1RF-1 and -2) were also established by recultivation of the 1N cells at the 16th passage (13.5 months later) through an in vivo passage; they were all characterized by active multiplication and growth with poor adhesion to the glass or floating in the medium after colony formation.
Comparison between two sublines, RMS-1N and RMS-1F1, was made with respect to cell morphology by means of light and electron microscopy, with special reference to tumorigenicity of cells and bioassay of culture fluids. The present results indicate that RMS-1F cells are malignant and release MSV with higher infectivity or oncogenicity than those of 1N cells. The virus released from the MSV-1F cells is capable of inducing tumors in both rats and mice indentical to those induced in them by the parent stock of MSV-M; osteosarcomas in rats and myosarcomas in mice, as well as in vitro transformation in rat embryo cells with one-hit kinetics.

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By means of the electron spin resonance method, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was found to be converted into free radicals on stirring or by photoirradiation. Production by the former method depended largely on the values of pH, the optimum values of which lie between pH 3 and 6. In photoirradiation, wavelengths longer than 340nm were effective, showing that the genesis of the free radical is correlated with n-π* transition at 400nm. N-Ethyl-, N-propyl-, and N-butyl-N'-nitro-N-nitrosoguanidines and N-methyl-N-nitrosourea also gave their free radicals by photoirradiation and their ESR signals were very similar to that of MNNG. On the other hand, no characteristic ESR signal was observed by the photoirradiation of N-methyl-N'-nitroguanidine. The significances of the free radical production in connection with the chemical reactivity and biological activities of MNNG were discussed.

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The repeated subcutaneous injections of a mixture of megestrol acetate and ethynylestardiol induced mammary fibroadenomas at a considerably high incidence in female rats of Wistar strain.

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Carbazilquinone could cure leukemia L-1210 in BDF₁ mice inoculated with less than 10⁶ cells. Further, the compound led the leukemic mice to cure even when the leukemia cells were implanted into DBA/2 mice. Therefore, Carbazilquinone might be potent enough to kill almost all the leukemia cells in vivo.

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The effect of eyclophosphamide on the proliferative capability of a mouse mammary carcinoma and combined treatment of the agent and ionizing radiation were studied. Possibility of using the agent to obtain a synergistic action with X-rays was discussed while the action was not demonstrated at the moment.

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A patient with ovarian adenocarcinoma was found to have lost all reactivities for 15 antisera to HL-A antigen when examined one day before her death. The loss of isoantigens controlled by HL-A in cancer is rare and its exact mechanism remains unknown.

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Carcinogenicity of dimethylnitrosoamine was tested by subcutaneous, intraperitoneal, or oral administration to three strains of mice. These treatments resulted in induction of hemangiomatous tumors in soft tissues especially in retroperitoneal areas. The incidence and localization of the tumors by the treatments were described.

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Protein moiety of the Pseudomonas aeruginosa endotoxin inhibited the growth of ascites sarcoma 180 at above 5μg/kg/day×5 and ED₉₀ was 40μg/kg/day×5, whereas lipopolysaccharide of the endotoxin was completely inactive against the sarcoma. This endotoxin was also active against Ehrlich ascites carcinoma.

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The transformed cells were examined for agglutinability to concanavalin-A in each growth phase. The cells at the plateau of cell growth decreased inagglutinability, compared with agglutinability of cells in the logarithmic phase.

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ICR female mice given diet supplemented with 0.025% 2, 7-fluorenylbisacetamide while nursing sucklings showed a unique susceptibility which led to unusual proliferation of mature and immature bile-duct cells.

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Application of a new method, consisting of enzyme histochemistry and radioautography, indicated persistence of enzymic immaturity for 17 weeks in some of the areas of hyperplasia, which was selectively labeled by ³H-thymidine after partial hepatectomy at the 9th week, while maturity in the majority of labeled lesions was proved.

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