Isozyme pattern of β-glucuronidase in normal rat liver and Yoshida sarcoma was investigated by DEAE-cellulose column chromatography. In both tissues, β-glucuronidase was separated into four fractions, although the distribution pattern was quite different from each other. The isozyme pattern was not significantly changed by treating Yoshida sarcoma with an antitumor agent, even at a dose with which the specific activity of β-glucuronidase was markedly increased.

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Host-mediated antitumor action of schizophyllan, prepared from the culture filtrate of Schizophyllum commune, was examined against four kinds of transplantable tumors in both ascites and solid forms. Schizophyllan is a polymer of repeating units composed of three or four β-(1→3)-linked D-glucopyranose residues to one of which is attached, through β-(1→6)-linkage, a side chain consisting of a single β-D-glucopyranose residue. The most significant results were obtained with 0.5-10mg/kg doses of schizophyllan on all the subcutaneously implanted tumors, i.e., sarcoma-37, sarcoma-180, Ehrlich carcinoma, and Yoshida sarcoma, accompanied with many complete regressions. On the other hand, the treatment failed to inhibit the growth of ascites tumors or to induce prolongation of life span, with the exception of ascites sarcoma-180, and also no inhibitory effect on Friend virus disease and spontaneous mammary carcinoma arising in Swiss mice. The mechanism of this action was considered to be host-mediated on the basis of lack of effect in contact test in vitro.

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Transplantation experiments were made on spontaneous hepatomas. Among eight hepatomas, two transplantable hepatomas were established, one of which, FSH-2417, reached 15th generations after four years. Their histological appearance was that of well-differentiated hepatocellular tumor and was well-preserved throughout the serial transplantation. The activity of glucose-6-phosphatase and ATPase, and the contents of cytochrome b₅ and P-450, which are specific components for the liver, were well maintained in the hepatomas.

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By intragastric instillation of 4-hydroxyaminoquinoline 1-oxide hydrochloride in ethanol solution, neoplastic lesions of the glandular stomach were induced in mice. These lesions included 3 advanced adenocarcinomas (4.5%), 19 mucosal carcinomas (28.8%), and one epidermoid carcinoma (1.5%) out of 66 effective animals. It is presumable that there is a continuity between the mucosal and advanced carcinomas.

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Effect of 18 synthesized compounds related to the powerful carcinogen, 4-nitroquinoline 1-oxide, on the synchronous cell division of Tetrahymena pyriformis strain GL was studied.
It was demonstrated that, when given just as the cells are entering into the first synchronous division, nine compounds which are carcinogenic induced nuclear derangement involving especially uneven distribution of DNA into sister cells. Nine other compounds which are non-carcinogenic showed no such effect.
Concerning the mechanism of the induction of unequal nuclear division, possible rôles of (i) nucleophilic reaction of the nitro group with division-related SH compounds and (ii) ready reduction of the nitro group to hydroxyamino group were considered.

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4-Hydroxyaminoquinoline 1-oxide was dissolved in dimethyl sulfoxide and 30 mice painted either with 4-hydroxyaminoquinoline 1-oxide alone, or with 4-hydroxyaminoquinoline 1-oxide, following a single application of 125μg of 7, 12-dimethylbenz[a]anthracene. With 4-hydroxyaminoquinoline 1-oxide alone, skin tumors were produced in 12 out of 30 effective number of animals 180 days after the first painting of 4-hydroxyaminoquinoline 1-oxide. The tumors consisted of 28 papillomas, 9 squamous carcinomas, and 1 carcinosarcoma. With 4-hydroxyaminoquinoline 1-oxide following 7, 12-dimethylbenz[a]anthracene, skin tumors were induced in 15 out of 30 effective number of animals. The tumors consisted of 13 papillomas, 3 squamous carcinomas, 1 fibrosarcoma, and 1 carcinosarcoma.

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A mode of the inhibitory action of three bacteriostatic agents, dehydroacetic acid, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, and p-hydroxypropiophenone, against carcinogenesis of 4-(dimethylamino)azobenzene (DAB) was studied in respect to their effect on the metabolic fate of the carcinogen.
Either one of the above three agents inhibited the combination of the carcinogen with the liver protein if administered simultaneously with the carcinogen. Dehydroacetic acid and p-hydroxypropiophenone delayed the tendency of the liver protein to combine with a smaller amount of the carcinogen as the carcinogenesis proceeds. The inhibitory potencies of these three agents paralleled their inhibitory potencies on the induction of hepatoma.
In an attempt to elucidate the mechanism of their inhibition on the formation of protein-bound dye and the development of deleterious changes of the liver in the rats fed DAB, studies were made on the fate of the carcinogen in the animal body, such as excretion, absorption, and distribution of DAB and its azo dye metabolites, and on the liver activity of metabolizing the carcinogen. Dehydroacetic acid exerted only a small effect on the metabolic fate of the carcinogen but p-hydroxypropiophenone decreased the concentration of the carcinogen and its azo dye metabolites in the liver. 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide decreased these concentrations not only in the liver but also in the blood, and it increased the liver activity of metabolizing the carcinogen if it was administered to the rat for more than 3-4 months.
These results and the findings from the study on the excretion of azo-dye metabolites suggested the participation of these three agents on the metabolic fate of the carcinogen, and these results and findings are discussed in relation to their inhibitory effect on the action of the carcinogen in the target organ.

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Japanese and Caucasian women in Hawaii have the same frequency of breast cancer in the childbearing period, but above 50 years of age the tumor is much less frequent in Japanese women. A survey of 92 Japanese women treated for this disease between 1954 and 1963 yielded a median age of 43 years, 72% of the patients being younger than 50 years of age. This age distribution differs from that of breast cancer in both U.S. white women and native Japanese women, each of which shows a far larger proportion of postmenopausal patients. The Hawaii Japanese women had smaller tumors and fewer axillary lymph node metastases than those of comparable women in Tokyo or New York. Follow-up studies indicate that 69% of these patients survived five years after diagnosis.

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Derivatives of 2-acylamido-6-purinethiol and/or 2-acylamido-9-alkyl-6-purinethiol were synthesized and the 2-acylamide derivatives were compared with the parent compound as to their antitumor activity and toxicity. The antitumor activity was assayed mostly with NF-sarcoma, which is known to be highly sensitive to this class of nucleic acid base analogs, but also using other types of tumors.
Among the 2-acylamide derivatives, formamide and especially isobutyroylamide derivatives were found to be the most active, but not markedly more active than the parent compound. A slight decrease in the toxicity was noted among the derivatives with high antitumor activity.

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The antigenicity of the substance depressing liver catalase in vivo (F) isolated from rat ascites hepatoma (AH-127) was identical with the substance (F') prepared from normal rat liver by the same procedure as that for F. Liver catalase in vivo depressing activity of F was hardly lost by incubation with the anti-F serum, but markedly inhibited by intraperitoneal injection of F' at the same time.

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In vitro culture of cancer cells from the lymph nodes with metastasis from gastric cancer was attempted to develop a method for drug sensitivity test of human cancer cells. Two long-term cultured cell lines were established from one of the 10 cases tested; the one was a monolayer culture line of epithelioid cells and the other was a suspendedc ell culture line of the free-floatingc ells. The cells of both cultured cell lines were identified with the cancer cells by light and electron microscopic examination. The suspended-cell line has been successively maintained in tissue culture during 190 days and serially subcultured for 34 generations, to date. It was designated as MC-8-S line.

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Effect of 7, 12-dimethylbenz[a]anthracene (DMBA) or 4-nitroquinoline, 1-oxide placed on the surface of mucosa of the glandular stomach combined with oral administration of N, N'-(2, 7-fluorenylene) bisacetamide (2, 7-FAA) or N-nitrosodiethylamine to male Donryu rats was studied in relation to the production of precancerous and cancerous lesions at the target area in the glandular stomach, as well as development of tumors in the liver and esophagus.
1) Many rats died of tumors of the liver and/or esophagus prior to the development of gastric carcinoma at the target area.
2) The lesions in the glandular stomach, i.e., scars and ulcers associated with or without heterotopic hyperplastic growth of glands, atypical glands, adenoma, polyp, carcinoma, and carcinosarcoma, were found only at the site of the focal treatment.
3) The lesions in the stomach were found in the highest rate in the group which received the local treatment with 4-nitroquinoline 1-oxide combined with the feeding of 2, 7-FAA. Combined treatment with DMBA and 2, 7-FAA or 4-nitroquinoline 1-oxide and N-nitrosodiethylamine also gave higher incidence of these lesions than the other treatments.
4) The local treatment with 4-nitroquinoline 1-oxide or DMBA placed on the surface of mucosa of the glandular stomach, which was performed at the beginning of the experiments, inhibited the development of tumors in liver caused by 2, 7-FAA feeding. The same treatment, however, did not inhibit the production of tumors in the liver and/or esophagus by the oral administration of N-nitrosodiethylamine.

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A study was made on the influence of salivary glands extirpation to the stomach carcinogenesis by 4-nitroquinoline 1-oxide. The incidence of malignant stomach tumor of the experimental group (salivary glands extirpated) was two-fold higher than that of the control group.

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A marked reduction of spontaneous leukemia incidence in a colony of AKR mice was observed. The fact that this AKR colony carried a potent mammary tumor virus suggests reciprocal interference of oncogenic activity between mammary tumor virus and leukemia virus.

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In vitro sensitivity of the cultured cells of human stomach cancer, AH-13 and AH-7974, to Mitomycin-C was tested. The IC₅₀ was different in each cell line. In ascites hepatomas, the in vitro IC₅₀ corresponded exactly to the in vivo drug-sensitivity estimated by survival prolongation.

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Female Donryu rats, 11 weeks of age, were given daily 15ml of drinking water containing 6 and 3mg of N-nitrosobutylurea for 125 and 167 days, respectively. High incidence of leukemia, probably erythroblastic in origin, was observed in both groups in addition to the development of hyperkeratosis of the forestomach and ear duct carcinoma in a few cases.

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