Mitosis in the Yoshida rat sarcoma cells growing in vivo was markedly suppressed by injection of 4-nitroquinoline 1-oxide. The following three types of chromosome abnormalitiesw ere observed after injection of the chemical. (1) Abnormal elongation of chromatids, observed within 3 hours after injection of the chemical, was accompanied by remarkable chromatid gaps. (2) Chromatid breakage (chromatid intrachange) was observed 4 to 12 hours after injection, showing the highest occurrence after 8 hours. The frequency of chromatid breaks increased linearly with the increase of dosage. (3) Chromatid translocation (chromatid interchange) wasmainly observed 12 to 48 hours after injection. The types and cause of chromosomal abnormalities caused by 4-nitroquinoline 1-oxide are discussed.

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In an attempt to elucidate the host mediated, tumor-inhibiting effect of polysaccharide fraction isolated from bamboo leaves, the properties of plasma protein, and immune response were compared between the polysaccharide-treated and normal control mice. There was a considerable increase in circulating globulin fraction in the polysaccharide recipients, and the plasma from the mice treated with the polysaccharide showed antitumor effect in vivo. It was found, however, that immune response of animals, in terms of the ability to produce antibody, was not markedly influenced by the administration of this polysaccharide.
Effects of certain other plant polysaccharides, without antitumor effect, were determined in the same way as those of the bamboo polysaccharide.

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N, N-Bis(2-chloroethyl)-N', O-propylenephosphoric acid ester diamide (cyclophosphamide), one of the derivatives of nitrogen mustard, is said to be almost inactive in vitro, and the agent becomes biologically active in vivo only on appropriate activation, which is thought to be accomplished probably by the liver.
The present investigation deals with the late effect including possible carcinogenic influence of the agent in normal mice, to whom a minute amount of the agent was repeatedly administered for a relatively long duration.
The results obtained indicate that cyclophosphamide appears to be activated in vivo, probably by the liver, and to be capable of inducing benign and malignant tumors predominantly in the lung, liver, and sexual organs of both sexes in mice.

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A study was made on how the host animal responds to tumor growth, with special reference to protein metabolism. The synthesis of plasma protein in tumorbearing rats was elevated to the same extent as in plasmapheresis, whereas the synthesis of muscle protein was depressed to the same degree as in rats fed on a protein-free diet. These changes could not be reproduced by the administration of a crude preparation of toxohormone. A marked decrease in the turnover rate of plasma protein was observed at a late stage in tumor-bearing animals.

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Electron microscopy was carried out on a transplantable lymphocytic leukemia and a reticulum cell sarcoma in C3Hf mice. The lymphocytic leukemia was presumably spontaneous in origin, and the reticulum cell sarcoma occurred in one of C3Hf mice inoculated with cell-free filtrate of lymphocytic leukemia. Thin sections from both transplants revealed virus particles with either electron-dense or electron-lucent centers in the intercellular spaces and in the cytoplasmic vacuoles. These particles ranged from 90 to 110mμ in outer diameter with nucleoids measuring 50 to 60 mμ, and appeared identical with other murine leukemia viruses. These findings suggest that virus is etiologically related to the development of reticular tissue neoplasms in low-leukemic C3Hf mice.
Furthermore, virus-like particles morphologically distinct from leukemia virus were observed in both transplants. Majority of them varied in size from 100 to 200mμ, and consisted of an electron-dense core and surrounding double membrane. Although the biological significance of these particles is unknown, they probably represent mycoplasma (pleuropneumonia-like organisms). Some of the ultrastructural characteristics of tumor cells are also described.

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The effect of N-(3-oxapentamethylene)-N', N"-diethylenephosphoramide (MEPA) on cells of the Yoshida ascites sarcoma was studied cytologically and cytochemically. The most effective dose of MEPA so far examined was 10mg/kg. A single intraperitoneal injection of MEPA at this dose induced tumor regression in 62% of rats examined. Higher doses were more carcinolytic, but toxic to the animals. MEPA produced an increase in average cell volume which reached a value of about 4×10³μ³ within 3 days, corresponding to an 11-fold increase in volume over untreated cells.
Chromosome aberrations induced were frequent in metaphasic cells during the compensatory recovery period of the mitotic rate. Aberrations observed were fragmentation, lagging, stickiness, filamentation, bridge-formation, translocation, and breakage. These changes are similarly found in cells affected by radiomimetic agents.
DNA content in tumor cells was measured by microspectrophotometry accord ing to the two-wavelength method. The average DNA content in tumor cells on the second and the third day of treatment was within the range of those found in untreated cells. This was not correlated to the increase in cell volume. PAS-positive granules increased in number and, at the same time, the oxidase activities demonstrated with the use of succinate and citrate as substrates increased along with cell volume, while glucose oxidizing activity became less.

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A microspectrophotometric evaluation of the DNA content of tumor cell nuclei was undertaken in 84 cases of human gastric carcinoma. As the control, the pyloric gland cells from two non-cancerous patients were used. The nuclei from the normal pyloric gland cells showed a standard DNA content of diploid value with a very limited degree of deviations from cell to cell. The mean amount of DNA in the tumor cell nuclei from each case of gastric carcinoma varied between the hypodiploid and hyperhexaploid range, and in 70% of the tumors, the mean values were found in the hyperdiploid to hypotetraploid ranges. There was no positive correlation between the mean DNA values and histological patterns or degrees of malignancy of the tumors examined.

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This paper deals with the antitumor effect of some new derivatives of sulfonic acid esters of aminoglycols, most of which were proved to be effective by primary screening against Yoshida sarcoma. However, N-methyl-bis(3-mesyloxypropyl)-amine hydrochloride (No. 838) was the only compound really effective in the prolongation of life-span of tumor-bearing animals. From the results obtained by using wide variety of experimental tumors, it seems to be one of the most promising compounds among alkylating agents synthesized.
Toxicological investigation was also carried out and its clinical test is now under progress.

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In the course of investigation on methanesulfonic acid esters of aminoglycols, a simple derivative, bis(3-mesyloxypropyl)amine hydrochloride (No. 864), was synthesized. Studies on its antitumor activity revealed a strong efficacy on naturally resistant experimental tumors, AH-7974 and AH-66, and leukemia SN-36 but not on strain of Yoshida sarcoma with acquired resistance. The present paper deals with the synthesis of No. 864 and its screening data so far obtained.

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Effect of radiation on tumor cells was studied quantitatively with vaginal smears of patients with uterine cancer in order to determine the sensitivity of cancer cells to radiation on the assumption that this would reflect host sensitivity as well as sensitivity based on the pattern of cancer cells per se.
The percentage of dyskaryotic tumor cells increased in a sigmoid fashion with dose by external irradiation with cobalt-60. The 50% tumor dyskaryosis dose, which may be identical with the 50% lethal dose of radiation, ranged from 500 to 2, 500r. The relationship between this index and prognosis is as yet to be determined.

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An inbred substrain of C3H mouse wasestablished and designated as C3H/HeNSa. In this strain of mice, transplantability of the mouse ascites hepatoma (MH-134, MH-129P, and MH-129F) and the mouse ascites tumor FM3A was very high. Characteristics of the mammary cancer incidence and metastasis in the animals of this strain are described.

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