The carcinogenic action of nitrosodimethylamine was tested by oral administration of 100ppm in basal diet for 16 to 92 days to DDD mice, and by subcutaneous injection of 0.15mg in 0.2ml of physiological saline into DDD and BALB/c mice once a week for 1 to 35 weeks. These treatments resulted in induction of lung adenomas and carcinomas, and benign and malignant hemangiomas mainly in the liver and soft tissues, and occasionally in the lung, kidney, and spleen, and also of leukemia. The incidence of hemangioendothelial sarcomas in soft tissues, especially pararenal and associated regions, was much higher in the animals receiving the carcinogen by injection. Histogenesis of hemangioendothelial sarcomas of the liver induced by nitrosodimethylamine is described.

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Intact and castrated male and female rats with alloxan diabetes were given 0.025% 2-diacetamidofluorene in the diet. Intact male rats given the carcinogen-containing diet developed hepatocellular carcinomas and cirrhosis in high incidence, whereas carcinomas and cirrhosis of the liver were not observed in intact male rats with diabetes. The development of hepatic lesions in intact or castrated females or castrated males was not influenced by the diabetes. It is felt that the animals with diabetes did not develop carcinomas and cirrhosis because of the lack of insulin and its ability to increase protein synthesis in the liver.

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The effect of 1.4% DL-tryptophan in the diet on tumorigenesis in the urinary bladder, liver, and esophagus of male Wistar strain rats receiving N-nitrosodibutylamine in their drinking water was studied.
Administration of N-nitrosodibutylamine with basal diet containing sucrose induced tumors of the urinary bladder and esophagus in all the animals tested and tumor of the liver with low incidence (33.3% of the animals). When tryptophan was administered with N-nitrosodibutylamine, tumors developed in the urinary bladder in all the animals, and in the esophagus in 11 of 12 rats (91.7%), but no tumor of the liver was found.
These results show that DL-tryptophan completely inhibited the development of liver tumors induced by N-nitrosodibutylamine, but did not affect the high incidence of urinary bladder tumors induced by N-nitrosodibutylamine. These results also suggest that DL-tryptophan has an antagonistic effect on hepatocarcinogenesis of rats induced by N-nitrosodibutylamine, or a protective effect against the toxicity of this chemical in rats, but that its effect is positively correlated with N-nitrosodibutylamine in induction of urinary bladder tumors.

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Antiserum, obtained by immunization of human gastric mucosal glycoprotein into rabbits and confirmed to give a specific precipitate reaction against gastric mucosa in the Ouchterlony assay, was employed for the immunofluorescence staining of gastric carcinomas. The undifferentiated carcinoma cells of carcinoma simplex, diffusely proliferating in the mucosa as well as in the submucosal and muscular layer, fluoresced intensely. On the other hand, well-differentiated carcinoma cells of adenocarcinoma in the mucosa were devoid of fluorescence, though the lessdifferentiated ones sprouting into the submucosal and muscular layer fluoresced well.
Such a glycoprotein material was recognized to exist as a normal gastric mucosal component rather in the less or undifferentiated gastric carcinoma.

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The construction, installation, care, and use of a new type of transparent chamber, adapted to the rat skin, are described for morphological and physiological studies of living microcirculation, referring to the microcirculatory studies on cancer metastasis.

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Assays of non-specific esterase during carcinogenesis of skin and in tumors of submaxillary salivary gland of the mouse were made and following findings were obtained.
1) Dedifferentiation of zymogram in carcinogenesis and tumor state demonstrated that the migration pattern is a simple form gathering toward the direction of the fast moving esterase-I accompanied by a lesser activity of esterase-II and esterase-III during tumorigenesis.
2) Epithelial tumors in the submaxillary salivary gland presented a specific pattern according to histological features of keratinization in tumor tissues-nonkeratinizing type of submaxillary salivary gland tumors showed a high active form of esterase-Ia which was resistant to eserine and diisopropyl fluorophosphonate, while keratinizing type exhibited active pattern of esterase-Ia and esterase-Ib, like carcinomas of the skin. Esterase-Ib was sensitive to both inhibitors.

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Antitumor activity of various compounds of tenuazonic acid analogs, 5-substituted 3-(1'-anilinoethylidene)pyrrolidine-2, 4-dione, was tested in vitro and in vivo. Among these compounds, 5-benzyl and 5-(p-hydroxybenzyl) derivatives were found to be highly effective against Yoshida sarcoma cells in vitro and Ehrlich ascites tumor in vivo. The latter compound was also active against Yoshida sarcoma and L-1210 in vivo. The optical activity of the active compound does not seem to concern the antitumor activity. Structure-activity relationship of these compounds was discussed.

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Hyperplastic lesions, especially areas and nodules of hyperplasia, developed in the liver of Donryu rats fed 0.03% 2-fluorenylacetamide (2-FAA) diet, were examined histochemically and histologically, and compared with hepatomas. Areas of hyperplasia showed a moderate to marked decrease in β-glucuronidase, glucose-6-phosphatase, canalicular ATPase, and phosphorylase activities, and slight to moderate decrease of acid and alkaline phosphatase activities, SDH activity, and glycogen level. Occasional increase was also observed in the activity of phosphorylase, canalicular activity of ATPase, and alkaline phosphatase. The enzymic deviation in the areas of hyperplasia lasted long, except that of more or less prominent increase in lysosomal or canalicular enzymes that occurred with time.
Nodules of hyperplasia showed principally similar histochemical features as areas. Only in the former, however, the decrease of glucose-6-phosphatase and canalicular ATPase and alkaline phosphatase, and glycogen levels were usually more marked. Occasionally increased β-glucuronidase activity was also observed in the nodules of hyperplasia.
When the histochemical features of areas and nodules of hyperplasia were compared with those of hepatomas, similarities were emphasized, although in some hepatomas abnormal staining patterns and variability of the levels of some enzymes within a lesion were observed. The histochemical findings indicate that the two kinds of hyperplastic lesions and hepatomas are to be classified in the same category so far as they are definitely and persistently deviated from normal liver cells.

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Responsiveness of hyperplastic lesions of the rat liver and hepatomas to partial hepatectomy was investigated by counting mitotic indices. Male Donryu rats fed 0.03% 2-fluorenylacetamide (2-FAA) or 0.06% 3'-methyl-4-(dimethylamino)-azobenzene (3'-Me-DAB) were used. Mitotic index 45 to 48hr after a two-third partial hepatectomy was obtained and compared to that before partial hepatectomy. Areas of hyperplasia showed highly elevated mitotic indices, while the nodules of hyperplasia, nodules with atypia, and hepatomas with relatively low mitotic level responded with moderate elevation of the indices. In general the responsiveness of the nodules decreased gradually with the growing size, but it never became completely negative. Three hepatomas with high mitotic level and a cholangioma revealed slight or no change in the mitotic index after hepatectomy. In the liver of rats fed 0.03% 2-FAA, the original mature liver cells were quite inactive as long as the carcinogen was administered, but 6 to 24 weeks after discontinuation of the carcinogen their responsiveness returned to the same or even higher level than that of the areas and nodules of hyperplasia. The hypertrophic liver cells and areas of small cell hyperplasia, which were prominent in 3'-Me-DAB experiment, were apparently reactive to partial hepatectomy even during administration of carcinogen.

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The glandular stomach of living rats was examined by X-ray to diagnose malignant tumors produced by administration of N-methyl-N'-nitro-N-nitrosoguanidine. Tumorous lesions were detected in two cases using a specially designed X-ray method. Lesions were diagnosed by observation of filling defects and irregularity of the wall or mucosal abnormalities. This method should be applicable in studies on the growth of experimentally produced gastric cancer in rats.

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N-Methyl-N'-nitro-N-nitrosoguanidine solution was infused as a carcinogen into the lumen of the large intestine of the rat through the anal orifice. By this simple new method, carcinoma and adenomatous polyp were produced in the large intestine with high incidence.

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Centrophenoxine markedly enhanced the antitumor effect of cyclophosphamide against ascites sarcoma-180 with less toxicity increase. Therapeutic index of cyclophosphamide was elevated from 9.6 to 19.5 by the presence of Centrophenoxine in a dose of 200mg/kg/day.

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Intestinal metalpasia of the stomach was detected by placing Tes-tapes after spraying 5% sucrose solution on the mucosal surface. The tapes in the area with intestinal metaplasia become green due to glucose released from sucrose by intestine-specific sucrase.

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