Es wird über Veränderungen des Stoffwechsels unter Sauerstoffüberdruckbeatmung unter Einfluss verschiedener stoffwechselwirksamer Hormone berichtet und gleichzeitig die strahlensensibilisierende Wirkung des Sauerstoffüberdrucks durch biochemische Untersuchungen im Tierexperiment bewiesen.

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Effect of anticancer drugs on DNA synthesis and mitotic cycle of rat liver cells during the period of regeneration after partial hepatectomy was investigated by autoradiography with tritiated thymidine and biochemical analysis. A single injection of Mitomycin-C or Chromomycin-A₃ depressed DNA synthesis and mitosis if the drug was given before extensive DNA synthesis took place. Cyclophosphamide or thio-TEPA did not depress DNA synthesis but suppressed cell division significantly. The inhibitory activity of Mitomycin-C proved most effective in comparison with those of other anticancer agents.

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A simplified method for determination of hormones responsible for breast cancer was studied using tumor slices in vitro. Uptake of ³²P into nucleic acid of tumor slices was elevated by the addition of dependent hormones. Mammary tumors of C3H mice are highly dependent on steroid hormones. ³²P uptake into nucleic acid of C3H mammary tumor was elevated by 17β-estradiol and cortisol, and was suppressed by progesterone and testosterone propionate.
Breast cancer patients were divided into three groups of hormone-dependent, hormone-independent, and hormone-sensitive. In hormone-dependent or -sensitive breast cancer, addition of the corresponding hormones influenced ³²P uptake into nucleic acid of tumor slices. From these results, the preferable postoperative treatments for breast cancer were suggested.

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Transplantable Yoshida ascites sarcoma cells of Donryu rat were treated with plasmin, and changes in the lysosomal enzyme activities of tumor cells were investigated. Both total and free activities of three lysosomal hydrolases, acid deoxyribonuclease, β-glucuronidase, and acid phosphatase, increased in the sedimentable fraction of tumor cells at 2 hours after plasmin treatment, while the total activities of acid deoxyribonuclease and acid phosphatase increased in the unsedimentable fraction at 1 hour after Mitomycin-C treatment. When treated with plasmin and Mitomycin-C, not only the total activity in the unsedimentable fraction, but also both free and total activities in the sedimentable fraction increased as compared to those obtained by treatment with Mitomycin-C alone. In the survival experiments, survival period of tumor-bearing rats following plasmin treatment was almost the same with the control group. The survival curve of the Mitomycin-C treated group was much better than that of the control group, and the combined treatment with plasmin and Mitomycin-C brought much longer survival periods than treatment with Mitomycin-C alone. From these results it was concluded that plasmin labilized the lysosomes of tumor cells in vivo, and that the cytocidal effect of Mitomycin-C was enhanced through the increased release of lysosomal enzymes by concomitant treatment with plasmin.

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Two fractions having thymidine kinase (ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21) activity were separated from tumor cells such as KB and Yoshida sarcoma cells by means of zone electrophoresis or DEAE-cellulose column chromatography, while only a single fraction of thymidine kinase was observed in normal cells such as rat bone marrow, spleen, and embryonic and regenerating livers. The pattern of thymidine kinase of the regenerating liver in electrophoresis was different from that of embryonic liver.

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Definite ¹⁴CO₂ evolution from glucose[1-¹⁴C], observed with the microsomefree supernatant fraction fortified with ATP and TPNH of Ehrlich ascites tumor cells, was highly dependent on oxygen, insensitive to Amytal as well as Antimycin-A, and slightly sensitive to dicumarol. ¹⁴CO₂ production was markedly decreased by dialyzing this fraction, but completely restored by adding the ultrafiltrate. The mechanisms for the generation of TPN from TPNH added externally in the microsome-free supernatant fraction were discussed.

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Skin tumor induction in thymectomized CFW mice was compared to that in sham-operated and unoperated control animals. In the first experiment, in which mice were treated with daily paintings of croton oil after urethan initiation, skin papillomas occurred fewer in number and later in appearance in neonatally thymectomized animals than in unoperated controls, although the first tumor appeared accelerated in the experimental animals. In the second experiment, with repeated paintings with 3-methylcholanthrene, skin papillomas appeared earlier in some of the thymectomized mice than in controls. The accelerated or suppressed induction of papillomas in these two experiments was also seen in sham-operated animals, so this is due probably to the neonatal surgical invasion to the host and not to the anticipated impairment of immunological development.
In contrast, skin carcinomas occurring in mice in the second experiment appeared earlier in the neonatally thymectomized than in the sham-operated animals. Six weeks, the time difference of the tumor appearance between these two groups, is so significant as immune-suppressing factors might be removed by the operation.
The data from these experiments suggest that immune mechanism, if any, may affect the induction of carcinomas but not of papillomas.

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Mannan fractions were prepared from five species of yeast, i.e., Candida albicans B-792, Candida albicans A-207, Candida stellatoidea, Candida utilis, and Saccharomyces cerevisiae. Each polysaccharide was chemically analyzed and examined as to their host-mediated antitumor activities against sarcoma-180 solid tumor in mice. The tumor-inhibiting activity of these fractions calculated from the weight of tumor at the end of 5 weeks were 99, 65, 82, 10, and 91%. The fractions from C. albicans A-207, C. stellatoidea, and S. cerevisiae contained only a trace of glucose, whereas hose from C. albicans B-792 and C. utilis showed a considerable glucose content. Some possibility of a relationship between the structural difference in the constituent polysaccharides and their biological activities was discussed.

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Relative frequency and mortality rate of various types of leukemia in Japan were studied on 3, 925 autopsied cases, comparing both clinical and pathological diagnoses, obtained from "Annual of Pathological Autopsy Cases in Japan" published during the period of 1958 to 1965. About 55% of all leukemia in Japan is acute granulocytic leukemia, followed by chronic granulocytic, acute lymphocytic, and acute monocytic leukemia. Chronic lymphocytic leukemia is less than 2%. Comparison of the mortality rate revealed that chronic lymphocytic leukemia was at least 39.3 to 91.8 times more in the U.S.A., Israel, and Sweden than in Japan, but other types were not so strikingly different. There seems to be a difference in prevalent type of leukemia in different countries, and to record accurate cell types and chronicity for comparison among genetically different populations may serve as a clue for etiological investigations in the future.

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1. Marked production of H₂O₂ was observed in vitro at pH 7.8 at 37° under aeration by 4-hydroxyaminoquinoline 1-oxide but not by 4-nitroquinoline 1-oxide or 4-aminoquinoline 1-oxide.
2. Catalase (H₂O₂:H₂O₂ oxidoreductase, EC 1.11.1.6) and peroxidase (Donor: H₂O₂ oxidoreductase, EC 1.11.1.7) eliminated H₂O₂ in the incubation mixtures of 4-hydroxyaminoquinoline 1-oxide.
3. The production of H₂O₂ by 4-hydroxyaminoquinoline 1-oxide was dependent on oxygen.
4. The production of H₂O₂ by 4-hydroxyaminoquinoline 1-oxide was lower at acidic and higher at alkaline pH. Marked destruction of H₂O₂ was observed at high alkaline pH and an optimum pH for the production of H₂O₂ was around 8.
5. The reaction between free radicals of 4-hydroxyaminoquinoline 1-oxide and oxygen may be involved in the formation of H₂O₂ by 4-hydroxyaminoquinoline 1-oxide.

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Frequencies of chromosome aberrations induced by 7, 12-dimethylbenz[a]-anthracene and urethan in hematopoietic cells of mice varied significantly with the age at chemical treatment and the strain of mice, whereas those by 4-nitroquinoline 1-oxide did not. Under the given experimental conditions, the susceptibility of mice to the induction of aberrations appeared to be correlated with their susceptibility to leukemogenesis. The potency of chemicals to produce the aberrations, however, did not necessarily seem to be consistent with their leukemogenic potency.

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Experimental evidence has been obtained for the involvement of charge transfer in the interaction between DNA and 4-nitroquinoline 1-oxide and related carcinogens. Examinations were made on the nature of hypochromic changes exhibited in the absorption spectra of DNA and deoxyribonucleosides by the presence of the following compounds: Quinoline 1-oxide, 4-nitroquinoline, 4-nitroquinoline 1-oxide, 4-nitroquinaldine 1-oxide, 6-chloro-4-nitroquinoline 1-oxide, 4-hydroxyaminoquinoline 1-oxide, and 4-nitropyridine 1-oxide. The spectral changes were characterized by two common features: (1) Hypochromic changes were produced in the shorter wavelength regions of spectra of DNA and deoxyribonucleosides, the greater part of longer wavelength side slopes of the original spectra remaining unaffected, and (2) in every case of mixed systems of carcinogenic quinoline derivatives, larger changes were produced with purine deoxyribonucleosides than with pyrimidine deoxyribonucleosides. The degree of hypochromicity was expressed in terms of percentage hypochromicity, and it was revealed that there exists a close correlation between degree of hypochromic effect and biological activities of the compounds examined. It was found that the percentage hypochromicity values of quinoline derivatives run parallel with the half-wave potentials reported by Kawazoe et al., and with the quantities of charge transfer computed by Nagata et al.

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In vitro cloning from the cultured Friend viral leukemia cells was made and all of over 100 clonal isolates did produce the Friend virus with a variety of infectivity. Eight low-titer clones were selected and their virus production was followed for more than 250 days. They all revealed a markedly increased virus production in the course of serial passage cultures. A variety of virus infectivity was also observed in sublines isolated by re-cloning from these clones. Extremely low virus-producers were isolated from one of the low virus-producing clones by repeated selective clonings, but they also all changed into high virus-producers by serial passage cultures. It was proved by clonal analysis of this cell line that Friend viral leukemia cells were essentially homogeneous in virus production, and that an amount of virus produced was not competently used as a marker of clones. This increased virus production in the clones was compared with the work of an attenuated leukemogenicity in later passages of leukemia virus-infected cultures.

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Nakahara-Fukuoka sarcoma was established to be constant in transplantability and uniform in growth, and suitable for use in screening test for antitumor agents. Its sensitivity to some of the known antitumor agents was also examined, and its high susceptibility to purine analogs was confirmed.

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A phenol extract obtained from primary liver tumor induced by N, N'-(fluoren-2, 7-ylene)-bisacetylamine was injected into newborn ICR mice. Liver tumors were found in treated mice at a rate of about 50% until 18 months after birth.

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