Newborn mice of dd strain received a single subcutaneous injection of cycasin (β-D-glucosyloxyazoxymethane) in a dose of 0.5mg/g (Group I) or 1.0mg/g body weight (Group II), within 24 hours after birth. In Group I, 15 out of 17 mice (88%) which survived beyond 150 days after injection, developed lung tumors and 11 mice (64%) developed liver tumors. Although neurological disorders were induced in mice of Group II and animals with severe ataxia died within a relatively short period, only slightly affected animals survived for a long period and 29 out of 35 mice (83%) had lung tumors and 13 mice (37%) had liver tumors.

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Transplantability of cultured mammary carcinoma cell line, FM3A/B, was reduced markedly during culture. After 100 serial passages in vitro of the cell line, which had grown out from a single cell, one out of 13 clones isolated from this cell line had a very low transplantability. Growth characteristics in vitro and modal number of chromosomes of this clone were similar to those of the clone with high transplantability. Possible immunological changes were discussed in connection with its low transplantability.

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The distribution of ³H-labeled 4-nitroquinoline 1-oxide in several vital organs was studied by a tracer technique after its oral administration. The administered radioactivity was excreted through both the fecal and urinary routes. At 24hr after dosing, the highest radioactivity was found in the stomach tissues and this tissue also accumulated greater radioactive substances than any other tissue for a long time. The radioactivity in the forestomach was about 82% of the total radioactivity in the stomach tissue and the specific activity was significantly higher in the mucosa of forestomach than in the muscle tissue of forestomach, and the mucosa and muscle of glandular stomach. Thin-layer chromatography of extracts of each tissue with acidic ethanol showed that the radioactivity was very low in the 4-nitroquinoline 1-oxide fraction and high in 4-aminoquinoline 1-oxide fraction. The treatment of tissues from rats dosed ³H-4-nitroquinoline 1-oxide 24hr previously, with trichloroacetic acid, organic solvents, and a proteolytic enzyme showed that the radioactivity interacted with proteins, and nucleic acids in the tissues was higher in the stomach tissue than in the liver and intestine.

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Adult mastomys of both sexes were administered subcutaneously with N-nitrosodimethylamine in a total dose of 2.0, 3.8, 5.4, 7.1, and 8.8mg for 10, 19, 27, 36, and 44 weeks. The liver lesions of the animals treated with N-nitrosodimethylamine were characterized mainly by peliosis hepatic and cholangiocarcinoma. However, the incidence and the latent period for induced liver tumor did not indicate a dose relation. The mean survival periods in the groups treated with N-nitrosodimethylamine for more than 36 weeks tended to be shorter than that of other groups. Incidence of stomach tumor in males was lower than that of untreated animals, but fluctuated in females. In addition, other tumors, such as five pituitary adenomas, one adrenal adenoma, and one thymic lymphoma were found.

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One hundred and forty-two adenomatous polyps were obtained from 89 cases of resected stomach and examined histologically, including 25 by complete serial sectioning and reconstruction method. The essential component responsible for the protrusion of the adenomatous polyps was proliferation of the ducts, not connected to the gastric glands. Among these proliferated ducts, a peculiar type of duct with eosinophilic epithelium having prominent nucleolus was frequently observed. These "eosinophilic ducts" were observed not only in the adenomatous polyps but also at the ulcer edges and over the erosion scars. Histogenesis of the "eosinophilic ducts" and morphogenesis of the adenomatous polyps were discussed.

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Radioiodinated fibrinogen was localized preferentially in the metastasized and invaded tumor tissue of Walker carcinosarcoma induced experimentally.
In the blood-borne metastasis to the lung of rats, there appeared no definite correlation between the number of metastasized tumor nodules and radioactivity in each lung. However, the micro- and macro-autoradiographic studies of pulmonary and hepatic metastases revealed some significant findings as follows:
(1) The clearly defined blackening of macroautoradiographic images with the increased density in its margin, corresponding to the metastasized tumor nodule.
(2) The localized distribution of grains within hepatic cells which were present close and adjacent to the proliferating tumor cells.
These autoradiographic findings suggested a possibility of an interaction of tumor and host tissues in the borderline region and it seemed most likely to result from the inflammatory reaction as a host defense mechanism.

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In order to elicit a relation between the synthesis of Epstein-Barr (EB) virus and the growth of host cell, effect of an antibiotic, Neocarzinostatin, on the Burkitt lymphoma cell line, P3HR-1, was examined. One μg/ml of Neocarzinostatin was sufficient to inhibit cell division but it induced a formation of giant cells. Percentage of EB virus-bearing cells in the Neocarzinostatin-containing culture was higher than that in the control culture, as revealed by immunofluorescence. The virus particle counting by electron microscopy showed that actual production of EB virus particles in the Neocarzinostatin-treated culture was remarkably higher than that in the control culture. No difference was observed by electron microscopy in the morphology of EB virus particles between the Neocarzinostatin-treated and control cells. Autoradiographic studies on the cell cultures in the presence of Neocarzinostatin indicated that the number of cells incorporating ³H-thymidine was much higher in the fluorescent (EB virus-bearing) cells than in the non-fluorescent cells. These results strongly suggest that Neocarzinostatin reduces or prevents the synthesis of host cellular DNA and the cell division but not the synthesis of viral DNA or formation of viral particles in the cells.

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The mechanism of lymph node metastasis, especially lodgement, passage, and growth of tumor cells in lymph nodes, was investigated serially by direct inoculation of various strains of rat ascites tumor cells into the testicular lymphatics of Donryu rats. It was observed that passage of tumor cells through lymph nodes did not occur until the nodes were almost invaded by growing tumor cells. Successful inoculation of a small number of tumor cells and lack of considerable reaction of lymph node cells to tumor cells indicated that lymph nodes may be in a sense a suitable soil for proliferation. Based on the findings obtained, the functions of lymph nodes were discussed as a barrier in metastasis formation.

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Gastric carcinoma was present in 326 of 2, 908 cases of autopsy performed during 1961-1968 on the fixed population (ST-100) of Hiroshima and Nagasaki.
The prevalence rate of gastric carcinoma was 11.7% in Hiroshima and 9.8% in Nagasaki. The findings obtained with regard to prevalence by sex, age, gross classification, histological classification, infiltration in the gastric wall, and metastasis to other organs and lymph nodes were similar to those reported in literature.
In general, no relationship was observed between prevalence rate of gastric carcinoma and radiation exposure, but some findings were suggestive of such a relationship. In Hiroshima and Nagasaki males autopsied during 1961-1964 the tubular medullary histologic type was found more frequently in the irradiated than in the control group. A suggestive relationship was also observed between exposure dose and the prevalence of histologically scirrhous type in Hiroshima males autopsied during 1965-1968. No difference was noted between the group exposed to 40 rads or more and the group exposed to less than 40 rads with regard to gross findings, size of tumor, infiltration of gastric wall, or metastasis to other organs and lymph nodes. These findings suggest the desirability of conducting a long-range follow-up study to accumulate a large number of cases and to determine whether these relationships are true or chance findings.

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Carbazilquinone, 2, 5-bis(1-aziridinyl)-3-(2-carbamoyloxy-1-methoxyethyl)-6-methyl-1, 4-benzoquinone, was tested for antitumor activity against lymphoid leukemia L-1210 in BDF₁ mice. The compound was remarkably effective against L-1210 following continued, intermittent, or single intraperitoneal administration. Effectiveness of the compound was compared with Methotrexate, Mitomycin-C, Cytoxan, and Trenimon following single and continued intraperitoneal administration which started 24hr after the intraperitoneal inoculation of L-1210 cells. It was found that both therapeutic ratio and maximum effectiveness of Carbazilquinone were the highest of those of other agents tested.
The compound also prolonged the life-span of the intravenously inoculated leukemic mice even in a terminal condition. The life-span of the treated mice was 13.5 days from the start of the treatment as compared to 1.5 days in control mice when the drug was given intravenously to the mice 5 days after intravenous inoculation of L-1210 cells. It was also effective on i.p.-i.v. system.
Further oral administration of the compound gave the leukemic mice more than two-fold increase in life-span over the untreated control mice.

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The capacity of nucleosides and nucleotides to inhibit adenine phosphoribosyltransferase in cell-free extracts of L strain mouse cells was studied with a radioisotopic assay. None of 12 nucleosides was active at a concentration of 1mM. Of 27 nucleotides tested at the same concentration, only AMP, ADP, ATP, dAMP, and one of eight preparations of GDP (a "sodium" salt) produced more than 25% inhibition. In contrast to AMP-5', AMP-2' or AMP-3' (1mM) did not inhibit the enzyme. At higher concentrations, dATP, dGTP, GTP, CTP, UTP, and dTTP were moderately active.
GMP and GTP (1mM) were about 10% as active as AMP and 50% as active as GDP (dipotassium), which was less active than GTP at a concentration of 9.6mM. When tested at the same time against the same enzyme preparation, seven preparations of GDP (mono-, di- or tri-sodium, or dipotassium) from six commercial sources produced from -2.2 to 17.8% inhibition at a concentration of 1mM, but from 26.8 to 47.8% inhibition at a concentration of 9.6mM.
Chromatographic analyses of nucleotide-inhibited enzyme reaction mixtures showed that guanine nucleotides were dephosphorylated more extensively than adenine nucleotides. However, the relatively low inhibitory activity of GMP was not attributed to dephosphorylation.
Inhibition by AMP and dAMP was competitive with respect to 5-phosphoribosyl α-1-pyrophosphate, whereas inhibition by GDP (dipotassium salt) was not strictly competitive, and was of the "mixed" type with respect to adenine.

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Serum iron level in mice was studied by using disodium 4, 7-diphenyl-1, 10-phenanthro-linesulfonate reagent. Decrease of Serum iron level was observed in tumor-bearing mice and also in normal mice after injection of isolated toxohormone.

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The sucrose gradient sedimentation profile revealed that Bleomycin induced DNA breaks in the mouse L cells after 30-min treatment of the culture. Double strand breaks required approximately 10 times as much concentration as for single strand breaks. The single strand breaks produced were rapidly rejoined during the post-treatment incubation.

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