Roentgen rays of 500R per week was irradiated to the stomach region of 28 young adult Buffalo rats for 20 weeks during ingestion of a diet containing 0.025% N, N'-2, 7-fluorenylenebisacetamide. Six cases of adenocarcinomas (28.6%), 12 cases of adenocarcinoma-like growths (57.1%), and 17 cases of foci composed of immature atypical tubules (81.0%) were found in the glandular stomach out of 21 effective experimental animals, while no neoplasms were observed in 24 rats of the two control groups. Severe atrophy of the glandular mucosae and intensely heterotopic adenomatous growth in the proximal ends of the duodenum were constantly found in the rats of expeirmental groups.
Histologically, gradual changes from foci composed of immature atypical tubules to obvious adenocarcinomas were noted in all the stomachs examined. From these findings, it is concluded that appearance of immature tubules in the atrophic mucosa is an initial change in malignant transformation of the gastric mucosa in this experiment.
By intraperitoneal injection of 1μCi/g body weight of ³H-thymidine 1 hour before the rats were killed, pattern of distribution of the labeled cells was entirely different between non-neoplastic and neoplastic lesions. In the latter, the labeled cells were found diffusely among all neoplastic epithelia.

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Periodical examinations were made on lactate dehydrogenase (LDH) during the course of lung carcinogenesis by 4-nitroquinoline 1-oxide in mice. The total LDH activity in the lung increased about 1.7 times that of the control group with cancerization and the activity in the tumorous portion increased 2.5 to 3.5 times. In LDH isozyme pattern in the lung, about 40% relative decrease in fractions I and II, and about 20% relative increase in fractions IV and V indicated the increase of M-type LDH activity. This tendency appeared more marked in the tumorous portion and in the embryonic lung. Both were similar in total activity and isozyme pattern of LDH.

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Ability of the chemicals to bind with DNA in Ehrlich ascites cells was studied with thirteen ³H-labeled 4-nitroquinoline 1-oxide derivatives in relation to their carcinogenic activity. A semiquantitative parallelism was found between carcinogenicity and chemical binding ability of the compounds.

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Determination was made of the acid mucopolysaccharide content in a tumor induced by subcutaneous imbedding of silicone in Sprague-Dawley rats. The acid mucopolysaccharides in fibroma and fibroadenoma proved to be hyaluronic acid and chondroitinsulfate B. Fibrosarcoma and fibrosarcoma transformed or being transformed from fibroma contained, in addition to these substances, chondroitinsulfate A. Only fibroadenoma additionally contained a very small amount of heparin or heparin-like material. No difference was found in the amounts of acid mucopolysaccharides contained in tumor tissue among silicone-induced tumors. A ratio of chondroitinsulfate to hyaluronic acid was the highest in fibroadenoma.

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A high level of resistance against transplantation of Ehrlich carcinoma cells or sarcoma-180 was induced successfully in ddY mice by intraperitoneal injection of tumor cells sensitized with the serum of rabbits immunized with the same tumor cells. The mice immunized with Ehrlich carcinoma cells were cross resistant against sarcoma-180 and vice versa. There was no cytotoxic activity against Ehrlich carcinoma cells in resistant mouse serum, but there was a suppressive activity against tumor growth. Cytotoxic antibody was found only in the serum of mice challenged twice with the intact tumor cells.

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Glial tumours are rather difficult material for karyological study. Chromosomes of three glial tumours in mice were investigated by a direct method using extremely diluted trypsin. Although no specific chromosomal changes common to mouse glial tumours were found, there was a tendency to become a tetraploid in the first few generations and then to settle down gradually in the hypotetraploid range with increasing number of marker chromosomes. The stemline karyotypes gradually changed by serial transplantation but still could be easily followed. They could help to characterize and define individual tumour lines at the cellular level.

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A change in the concentration of embryo-specific serum α-globulin (α-fetoprotein) was studied in the serum of rats during ontogenesis, in the serum of gestating female, and in the serum and ascitic fluid of rats bearing transplantable ascites hepatoma.
Scrum α-fetoprotein concentration in fetus decreased 2 to 3 days after birth to approximately one-half of the prenatal level and disappeared in 5 weeks. In the serum of gestating rats α-fetoprotein appeared in a low concentration and disappeared within 1 week after delivery.
α-Fetoprotein was also detected in the serum and/or ascitic fluid of rats bearing some transplantable ascites tumor. Twenty-six out of 78 ascites hepatoma cell lines tcsted were found to be α-fetoprotein-producing lines. α-Fetoprotein was detected in one of 5 Morris hepatomas and in some sublines derived from Yoshida sarcoma. α-Fetoprotein was detected also in the extract of α-fetoprotein-producing tumor cells.

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Distribution of the in vivo liver catalase-depressing substance [toxohormone(liver catalase)] in the cells of Rhodamine sarcoma of rats, was examined.
1) Intracellular particles of Rhodamine sarcoma were centrifugally divided into nuclear, mitochondrial, and microsomal fractions. Each of these fractions was individually injectded into mice, and catalase activity was measured with the homogenates of the livers. The in vivo liver catalase-depressing activity was the highest with nuclear fraction. Mitochondrial fraction scarcely showed the activity, while the depressing activity of microsomal fraction varied from one preparation to another. The fractions prepared from tumor tissues freshly obtained had significantly lower activity than those prepared from tumor tissues stored in frozen state. Probably, during the period of storage, particle complexes containing the depressing substance are dissociated into particles of smaller sizes (equivalent in size mostly to microsomes).
2) Nuclear fraction from dorsal muscles of normal rats showed the depressing activity, but not that from the livers.
3) Nuclei isolated from tumor tissues showed the depressing activity. When they were further divided into fractions of chromatins and nucleoli, the former fraction was active, but not the latter fraction.
4) It is concluded that the depressing substance is at least mostly present in the nuclei of the cells of Rhodamine sarcoma and dorsal muscle, localized in the chromatins.

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Urethan was administered to suckling rats in order to disclose its neoplastic potentialities in their various tissues. Male and female rats of Buffalo and Long-Evans strains were given five weekly, subcutaneous injections of urethan in a dose of 1mg/g body weight, beginning at 7 days of age. Untreated rats of both strains served as controls.
Seventy to 100% of the treated rats of both strains had one or more primary tumors at the time of death. A large strain difference was observed in the susceptibility of various organs to urethan carcinogenesis between Buffalo and Long-Evans strains. In Buffalo strain, the lymphoreticular tissues, mammary glands, and liver were the target organs, while the kidneys were the most susceptible in Long-Evans strain. Three B-cell adenomas of the pancreatic islets were also found in the treated rats of both strains.

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A 55-year-old businessman was admitted because of left chest pain with expectoration of mucous sputum. After hospitalization for about 4 months, he died of exacerbation of the primary lung cancer. Autopsy revealed a tumor of poorly differentiated adenocarcinoma in the left lung with widespread metastases. With biochemical and immunological techniques, alkaline phosphatase in the lung cancer tissue, serum, and other organs was analysed. It was found that alkaline phosphatase in the lung cancer tissue was heat stable and sensitive to L-phenylalanine, and was also essentially the same with the placental alkaline phosphatase isoenzyme in the biochemical and immunological characteristics. However, no such isoenzyme could be detected in his serum. Various enzymes other than alkaline phosphatase were also analysed with the tissues of this patient, but no particular changes were observed.

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Antitumor activity of the newly synthesized phenothiazine compounds, substituted with haloacetyl group at 10-position, was examined against ascites sarcoma-180. Chloro-, bromo-, and iodo-acetylphenothiazines were found to be active, but fluoroacetyl derivative was not. Di- and tri-haloacetyl derivatives and others (17 compounds) were all inactive. Therapeutic indices of the former three active haloacetylphenothiazines were high, being 2.0 for chloro-, 6.4 for bromo-, and 5.2 for iodo-acetylphenothiazines as compared with 2.0 or less for the reference compounds. The toxicity of haloacetic acid was reduced by combination with phenothiazine as expected.

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The fluorescein isothiocyanate-conjugated antibody against the intestinal mucosaspecific glycoprotein was employed for the immunohistological demonstration of this glycoprotein in gastric carcinoma and intestinalized gastric mucosa. It was found to be distributed abundantly in goblet cells in intestinalized gastric mucosa but not in any cells of normal gastric glands. It was demonstrable in some of carcinoma cells of carcinoma simplex type and especially in signet ring cells, correlating well in the distribution with their alcianophilic mucous materials. It was, however, devoid in those of adenocarcinoma type having a well-differentiated glandular structure within the mucosa, though it appeared in the less-differentiated ones sprouting into the submucosal or muscular layer.

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The pyruvate kinase present in extracts from variuos tissues of rats has been separated into five pI-isozymes by isoelectric fractionation, the isoelectric points (pI) of which are 5.4, 6.1, 6.5, 7.4, and 7.8. Extracts from skeletal muscle, heart muscle, and brain contain only pI 7.4-isozyme, whereas extracts from liver, spleen, lung, erythrocyte, kidney, and Rhodamine sarcoma contain three to four different pI-isozymes. Of the pI-isozymes present in the extract from each kind of tissue, the pI-isozyme highest in relative activity is pI-5.4-isozyme for liver, pI 6.5-isozyme for spleen, lung, and erythrocytes, and pI 7.8-isozyme for kidney and Rhodamine sarcoma. The kinetic characteristics of the five pI-isozymes are different from one another. Growth of the tumor on the back of rats brings about a significant increase in the activity of pyruvate kinase in the livers; the pI 6.1-isozyme increases, whereas the other pI-isozymes are hardly influenced. When a preparation of chromatin from Rhodamine sarcoma is injected into rats, the activity of pyruvate kinase in the livers increases to a significant extent; approximately 60% of the increased activity is due to the pI 7.8-isozyme, the remainder to the pI 6.1-isozyme.

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The polynucleotide lipase activity changed during regeneration of the rat liver reaching a maximum by 37hr after partial hepatectomy. The increase in activity indicates the participation of the lipase in DNA synthesis. Contrary to ligase, the endonuclease activity was minimum at 37hr. The decrease in the nuclease activity suggests that the change of this enzyme level may also take part in the DNA synthesis. Higher ligase activity in spleen and ascites hepatoma, AH-130 and AH-7974, than in the liver was observed, and the nuclear extract exhibited high activity. ATP-dependent ligase of regenerating liver and that of spleen were separated into two fractions by phosphocellulose column chromatography. Most of the ligase activity of ascites hepatoma AH-130, however, was recovered in a single peak containing ligase-AMP complex. All these fractions were capable of rejoining the nicked DNA.

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Rat leukemias induced by N-nitrosobutylurea were examined with an electron microscope. Virus particles morphologically identified as the type-C particles were observed in the primary, transplantable, and cultured leukemias from WKA/Mk rats. Possible significance of the appearance of the virus particles in the rat leukemia is discussed.

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The mutagenicity of 4-nitroquinoline 1-oxide (4-NQO) and its metabolite, 4-hydroxy-aminoquinoline 1-oxide (4-HAQO), was tested in the ad-3 system of Neurospora crassa. After a 2-hr treatment of conidia with 4.0×10^-8M 4-HAQO the mutation frequencies were found to be significantly higher (p<0.01) than the average spontaneous mutation frequency. The mutation frequencies for both compounds increased with increasing doses. It appears that both compounds are potent mutagens in Neurospora crasse.

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The treatment of 3T3 cells with trypsin, similar to the transformation of the cells with SV40, increased the agglutinability of the cells by ten phytoagglutinins non-specific for human blood groups. Similar increase of the agglutinability by several kinds of phytoagglutinins was also observed for SV40-transformed 3T3 cells after trypsin treatment.

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The direct evidence has been presented that the immunological capability of thymus-derived cells is markedly impaired in tumor-bearing host as determined by their helper activity for anti-hapten antibody response.

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A hypoalbuminemic substance was partially purified from Ehrlich solid carcinoma by gelfiltration on Sephadex G-150. This substance displayed significant decrease in serum albumin of mice and its hydrolysate was composed of hexose, hexosamine, and 18 kinds of amino acids.

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Activity of cyclocytidine was reduced in intraperitoneal treatment to two-thirds of that by oral route, whereas that of aracytidine by intraperitoneal treatment was reduced to one-tenth of that by oral route. Influence on therapeutic ratio was less in cyclocytidine. Cyclocytidine is markedly advantageous over aracytidine in oral treatment.

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