In order to illustrate the carcinogenesis of various carcinogenic aromatic compounds uniformly at a molecular level, extension of the theory of Birks was investigated; the overlap integral J of the resonance transfer between aromatic amino acids and 85 kinds of carcinogenic aromatic compounds or 77 kinds of noncarcinogenic aromatic compounds was calculated. J values of carcinogenic aromatic compounds were compared with those of noncarcinogenic aromatic compounds and the J values of carcinogens were found to disperse in some constant region. The relationship between J values of carcinogenic aromatic compounds and their carcinogenic activity was examined and the rank correlations were found to be highly significant only in the case of tryptophan.

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Quantitative analysis was made on uninterrupted transpulmonary passage of cells, employing seven strains of transplantable tumor cells.
When a large number of tumor cells are injected intravenously, some mice die instantaneously and the others survive. The cause of instantaneous death was attributed to the pulmonary embolism by tumor cells, while the uninterrupted passage of cells through the lungs was noted, by means of histological and physical, especially electrocardiographic, examinations.
Number of tumor cells neccessary to cause instantaneous death by pulmonary embolism (LD₅₀) was characteristically different by the injection time and each tumor strain employed.
The largest number of tumor cells which could pass through the lungs during one minute was calculated from the values of LD₅₀ in each velocity of injection. It was noted that the number of passing cells was quite different with each strain of cells. For example, the largest was 86.7×10⁶ of SN36 tumor cells, while the smallest was 2.2×10⁶ of AH-66F. Such difference was discussed in correlation with the size of diameter in each strain of cells.
Based on the results from the experiments and reviewing the past literature, the mechanism of hematogenous metastasis was discussed, emphasizing the significance of circulating tumor cells in the blood stream.

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The specific gravity of rat liver cells decreased when the animals were administered N-nitrosodiethylamine. The range of variation becomes more conspicuous as the hyperplastic lesions progressed in the liver.

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Bleomycin has produced fairly specific ultrastructual alterations, including the reduction of chromatin in the nuclei, nucleolar segregation, the decrease of ribosomes, and other cytoplasmic degenerative changes in the 3-methylcholanthrene-induced mouse epidermal carcinoma cells. These alterations appeared to be related to each other and were assumed to be the morphological manifestations of the antineoplastic action of Bleomycin.

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Aromatic amines were studied by means of the electron spin resonance (ESR) method. 2-Amino-1-naphthol, 1-amino-2-naphthol, N-hydroxy-1-aminonaphthalene, and N-hydroxy-2-aminonaphthalene, which have been known to be carcinogenic, were found to produce a large number of free radicals in organic solvents and in aqueous solution. The free radical production depended on the pH values, and different kinds of free radicals were produced in acidic and alkaline solutions. On the other hand, non-carcinogenic aromatic amines and naphthols did not produce any free radical. Such a distinct parallelism between the free radical production and carcinogenicity suggested that the free radical was concerned in some way with carcinogenesis by aromatic amines.

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Two derivatives of 4-nitroquinoline 1-oxide were tested to determine whether or not they could summate the effect of submanifestational dose of 4-nitroquinoline 1-oxide. In the present summation experiment, number of tumors were produced by 4, 7-dinitroquinoline 1-oxide when applied after submanifestational dose of 4-nitroquinoline 1-oxide. 3-Mehtyl-4-nitroquinoline 1-oxide had been reported as noncarcinogenic but its carcinogenicity was proved by the present summation method.

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Studies on the incidence of karyotypically distinct cell populations were carried out on 93 primary rat leukemias induced by pulse doses of 7, 12-dimethylbenz-[a]anthracene. Although the leukemia cells were found to be of multiple 'clonal' origin, analysis of stemline cells in each leukemia clearly demonstrated the predominant growth of leukemia cell with trisomy of the largest telocentric chromosome (C-1) and the cell with normal karyotype. In a total of 103 stemlines examined, 32 (31.1%) involved C-1 trisomy and 48 (46.6%) had normal karyotype. It must be emphasized, however, that the former showed maturation toward erythroblasts, whereas the latter constituted various types of leukemia. Possible rôles of immunological and humoral environments of the hosts playing in neoplastic growth of the specific cell populations and the relationship of chromosomal abnormalities in the rat leukemia cells to the neoplastic state of the cells are discussed.

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Inactivation of the transforming activity of B. subtilis DNA caused by carcinogenic 4-hydroxyaminoquinoline 1-oxide was found to be protected by the presence of simple organic compounds such as dioxan, alcohols, etc., in the reaction mixture. The protection mechanism can be considered to involve scavenging or quenching of the active reactant produced from 4-hydroxyaminoquinoline 1-oxide during the inactivation process, competitively with the reaction with DNA molecule. The active reactant concerned here was assumed to be free radicals produced probably by homolytic cleavage of N-O bond in hydroxyamino group. Most of the components of nucleic acid, such as nucleosides, sugars, etc., showed more or less protective effect, indicating that the free radicals concerned may react with various sites of the nucleic acid molecule.

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Intravenous 4 pulse-doses of 7, 12-dimethvlbenz[a]anthracene were given to both adolescent and adult female mice of CF-1 strain. Leukemia was induced in high yield, especially in the younger group, 33 out of 34 or 97.1%, and 23 out of 28 or 82.1% in the older group by 153 days after the first injection. Thymus was the organ most involved by leukemia. Ovarian tumor was found in both groups and the tumor was always microscopic in size in the younger group whereas 5 out of 11 tumors were over 0.4cm in diameter in the older group. Mammary cancer was a rare kind of tumor in both groups. There was a strong inhibition of ovarian function after pulse-doses of the hydrocarbon detected by examination of vaginal smear. Size distribution curves of cells in peripheral blood were made and they are considered to be useful to make diagnosis of leukemia type.

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A nuclear magnetic resonance study is made on the interaction of the carcinogenic 4-nitroquinoline 1-oxide with deoxyribonucleosides and their related compounds in deuterated dimethyl sulfoxide by following the proton chemical shifts of the latter compounds as a function of 5, 6, 8-trideuterated 4-nitroquinoline 1-oxide concentration. It is shown that the NMR signals of the ring and amino protons of purine deoxyribonucleosides and the NH proton of deoxythymidine are shifted more or less to higher field in the presence of the N-oxide compound. In the case of mixed systems of purine deoxyribonucleosides and 4-nitroquinoline 1-oxide, it is presumed that stacking-interactions are more favorable than cross-interactions. Particular attention is given to the fact that the hydrogens which are responsible for the pairing of complementary bases in DNA were affected by the carcinogen. Visible difference absorption spectra, characteristic of charge-transfer bands, of mixed systems of purine deoxyribonucleosides and 4-nitroquinoline 1-oxide in dimethyl sulfoxide solution are also presented.

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The changing mortality rates of childhood leukemia in Japan were studied for the period of 1947 to 1966. There was a decrease in the mortality rates of under 3 years of age but a continuous increase between 3 and 4 years of age. The peak of the rate has been in the 3-year age group since around 1957, and a decline in the rate was first seen in the under 1-year age group following the peak in 1960. The mortality rate in the group from 5 to 14 years of age appears to be still increasing, but the rate of increase has declined since early 1960's. The rate of increase has been larger among females than among males in all age groups examined during the study period. The decline of mortality rate in children under 3 years of age is possibly due to the combined effect of a decline in the incidence and prolongation of survival time. However, the peak of the mortality rate at 3 years of age is largely due to the high incidence of leukemia at this age, and probably to the prolongation of survival time, which shifts death age of patients to 3 years old from under 3 years of age. The difference in these phenomena between Japan and U.S.A. is discussed.

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Two tissue culture cell lines designated OUMS-1 and OUMS-2 were established from each spleen of two BALB/c mice with Rauscher leukemia in the erythroblastic stage. The OUMS-1 cell line has been carried through 125 passages for the past 18 months, during which cellular morphology suggestive of erythrocytic maturation was observed, while the OUMS-2 cell line underwent neoplastic transformation after 6 months in vitro. The solid tumors resulting from implantation of the transformed OUMS-2 cells were spindle cell sarcomas which were serially transplantable in adult BALB/c mice. Bioassays of the supernatant fluids from both cultures induced Rauscher leukemia in suckling mice. However, there was some reduction of the leukemogenic activity after prolonged cultivation. Cell-free extracts of the transplantable tumors were less leukemogenic. These bioassay data were in parallel correlation with the number of type C virus particles observed by electron microscopy.

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The Vero cells were transformed by the Schmidt-Ruppin strain of Rous sarcoma virus. The transformed Vero (Vero-R-I) cells induced tumors in chicks and hamster cheek pouches. The tumor-inducing capacity of Vero-R-I cells in chicks, however, tended to decrease with successive passages.

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The incidence of thymic lymphoma in low-leukemic (C3Hf×AKR)F₁ hybrids was greatly increased after subcutaneous implantation of thymus, spleen, or mesenteric lymph node from 5-month-old, non-leukemic AKR mice. The mechanism of the tumor development was suggested to be mediated by a leukemia virus present in these grafts.

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Histological and hematological findings reflecting the radiomimetic biological effect of the new scirpene metabolites, nivalenol and nivalenol 4-O-acetate, from Fusarium nivale on the proliferating cells of the animals are described.

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³H-Pseudouridine was injected intraperitoneally into rats during the course of liver regeneration. The livers were removed and fractionated into chromatin, nucleolus, and cytoplasm. RNA was extracted from these fractions and its radioactivity was measured. Practically no appreciable amount of radioactivity was detected.

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By subcutaneous injection of 2-nitroquinoline in lecithin solution, lung tumor was induced in 4 out of 9 mice of ICR strain. They were carcinoma (33%) and adenoma (11%).

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