Sodium pentobarbital was injected in controls and the mice with spontaneous tumor. The mice were sacrificed at 5, 10, 15, 20, 25, and 30min after the injections and the levels of active pentobarbital were measured in the brains and plasma of both groups. The levels of unmetabolized pentobarbital in the tumor-bearing mice in both brain tissue and plasma were higher than in the controls, suggesting an impaired metabolism in the tumor-bearing mice resulting in quantitatively higher levels of active pentobarbital. However, the mice in both groups, tumor-breaing and control, wake up at the same level of active pentobarbital in the brain. In the tumor-bearing animals, it takes the active pentobarbital a little longer to reach that level and hence the prolonged sleeping time. The conclusions drawn from this study are:
1) There is an impaired metabolism of pentobarbital in tumor-bearing mice possibly caused by a tumor secretion such as toxohormone.
2) The possibility of an increased sensitivity of the brains of tumor-bearing mice to pentobarbital seems remote.
3) The possibility of increased blood-brain permeability due to the presence of a tumor also seems remote.

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Immunohistological studies were carried out on gastric and rectal carcinoma, using the fluorescein isothiocyanate-labeled antibody against placental alkaline phosphatase. The placental tissue exhibited the fluorescence most intensely in the outer cell borders of the syncytiotrophoblastic cells, and to a lesser degree in the inner cell borders and within the syncytium, with an essential agreement in the location to that found by the usual histochemical method. Other normal human tissues did not show the fluorescence.
In all cases of gastric carcinoma (28 cases) and rectal carcinoma (17 cases) examined, irrespective of the histological pattern, the fluorescent carcinoma cells were demonstrated at least in part. Among carcinoma cells arranged in the same histological pattern, some of them were fluorescent while others were not. Fluorescence appeared intensely localized along the cell border or diffusely within the cytoplasm. The intestinal metaplastic epithelium, stromal elements, and endothelial cells of blood capillaries, possessing high enzyme activity, were devoid of specific fluorescence. Sharp distinction in isoenzyme pattern between carcinoma and intestinal metaplasia was demonstrated.

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In vitro methylation of Escherichia coli t-RNA by enzyme preparation mainly from AH-108A and normal liver had been studied from ¹⁴C-methyl incorporation and distribution of the radioactivity in methylated bases. Crude enzyme preparation from the hepatoma exhibited about 4-fold higher level of methylation than the corresponding preparation from normal liver. There were subtle differences in optimum pH of both enzyme systems in the presence and absence of hydrochloride or carbonate of guanidine. The effect of guanidine carbonate was inhibitory. It is suggested from further experiments that the effect was principally due to its HCO₃^-. Methylation patterns were modified by varying of pH values and in the presence of guanidine carbonate. The carbonate raised the relative content of methylated guanines as the reflection of decrease in other methylated components. Composition of four methylated guanines showed that major products of the in vitro methylation were N²-methylguanine and N²-dimethylguanine, and the content of the latter was much higher in the reaction products by the hepatoma enzyme. Significance of higher levels of methylases catalyzing N²-dimethylguanine formation in hepatoma and 2-O-methylribose formation in normal liver cells is discussed.

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The oil-attached cell-wall skeletons of mycobacteria, nocardia, and corynebacteria, and peptidoglycolipid of Mycobacterium tuberculosis Aoyama B weree valuated for antitumor activity in the prevention of tumor growth of melanoma-B16, mastocytoma P815-X2, and EL-4 leukemia in syngeneic mice. When tumor growth was suppressed, specific and systemic tumor immunity to a subsequent tumor challenge was always demonstrated in mice. It was found that specific tumor immunity was induced by the intradermal injection of a mixture of oil-attached BCG cell-wall skeleton and irradiated or Mitomycin-C treated mastocytoma-P815 cells in syngeneic mice. The intravenous injection of oil-attached BCG cell-wall skeleton prevents the induction of lung cancer in rabbits by the instillation of a mixture of 3-methylcholanthrene and 4-nitroquinoline 1-oxide in rabbit plasma.

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The binding in vivo of ethionine with RNA, nuclear proteins, cytoplasmic proteins, and with DNA of rat liver, using high doses of carcinogen, is evidentiated. The binding in vitro to DNA is microsome-dependent; it is higher using polynucleotides as acceptors, under the same experimental conditions. Acid hydrolysis performed on DNA and poly-A after incubation in vitro leads to radioactive compounds, not coincident with 7-ethylguanine.

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A series of in vitro experiments have been carried out with the commercially available anticancer drugs in order to find which drug, when used in the acidic condition induced by tumor cell glycolysis, displays the strongest tumoricidal activity not to be expected from the conventional mode of administration. For this purpose, Ehrlich ascites tumor cells were incubated, without shaking, together with the test drug dissolved in various vehicles such as 5% aqueous glucose solution, 5% glucose in phosphate buffer, and phosphate-buffered saline. The cytocidal effect of these drugs on the tumor cells was assayed by transplanting the treated cells intraperitoneally in mice.
Among the drugs tested, Carbazilquinone revealed the strongest cytocidal effect, especially when dissolved in aqueous glucose solution but not in other vehicles. This result shows that Carbazilquinone has responded to our anticipation as being cytocidally the most effective when employed in combination with cancer cell glycolysis, probably because of its chemical composition of containing aziridine groups.

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The specific binding capacity of the estrogen receptor to tritiated estradiol was measured in the rat mammary cancer induced by 7, 12-dimethylbenz[a]anthracene and the capacity of each tumor was compared with its response to oophorectomy. The bound radioactivities of 14 concentrations of tritiated estradiol with a fixed amount of 2, 000g tumor supernatant were separated from the free by a dextran-coated charcoal method. The specific binding capacity of each tumor was estimated with the aid of the association constant (Ks) and the concentration of binding sites ([Ns]) obtained by Baulieu's proportion graph method. The estrogen receptor was found by this method in 19 of 30 tumors, with mean Ks of 5.7±1.6× 10¹⁰M^-1•g (of protein) and mean [Ns] of 2.2±0.6×10^-12M•g^-1, All of 12 rats with hormone-dependent (responsive to oophorectomy) tumor had obviously the receptor in the cytosol. Six out of 9 rats whose tumors showed intermediate response contained the receptor. Eight of 9 rats with hormone-independent tumor had no estrogen receptor. Thus a good correlation was obtained between the presence of the receptor and response to oophorectomy in the mammary cancer.

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Morphological changes of the urinary bladder epithelium of rats induced by N-butyl-N-(4-hydroxybutyl)nitrosoamine were studied by scanning and transmission electron microscopy.
Transmission electron microscopy showed that cells of normal bladder epithelium had an asymmetric unit membrane and fusiform vesicles, tonofilaments, and many polysomes in their cytoplasm. In regions of focal hyperplasia, multilayers were seen with clear and dark cells. Regions of papillary carcinoma showed considerable variation, with dark and clear carcinoma cells, invagination of the cytoplasm, bundles of thin filaments, transformation of the nuclei or nucleoli, and disappearance of fusiform vesicles.
Scanning electron microscopy showed that the surface membranes of cells of normal bladder epithelium were smooth with a network of fine ridges. Two different types of surface were seen in regions of focal hyperplasia; in one type, cells were mostly flat but in places hemispherical cells protruded, while in the other type, the surface cells looked like cobble stones with microvilli. In areas of papillary carcinoma the surface was formed from various sized hemispherical cells. The surface membrane had numerous complex microvilli, unlike normal bladder epithelium which had no microvilli.

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A continuous infusion of partially purified mouse mammary tumor antigen (MM antigen) for 10 days easily gave C3H/He mice a resistance to the challenge of an MM-102 ascites mammary carcinoma, originally developed in a C3H/He mouse and transformed into ascites form. These mice had no detectable antibodies to the antigen at this stage, but succeeding intraperitoneal challenges of the tumor cells caused rapid antibody response up to a very high titer after 6th challenge. In the final stage, the mice resisted the challenge of as many cells as 1×10⁸/mouse.

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Histopathological studies were made on tumorigenesis induced in rat liver by polychlorinated biphenyls. In the present experiments polychlorinated biphenyls induced nodular hyperplasias in rats, and marked cholangiofibrosis was seen in rat liver. However, the chemicals did not induce hepatocellular carcinomas.

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The effect of local application of N-methyl-N'-nitro-N-nitrosoguanidine into the brain was studied in C3H and C57BL mouse strains. Tumor was not induced in the brain but various kinds of tumor were induced in other organs in animals surviving over 7 months after the treatment.

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A protein-bound polysaccharide, PS-K, was isolated from Coriolus versicolor (FF.) QUEL of Basidiomycetes and found to be effective against mouse sarcoma-180 and rat ascites hepatoma AH-13 when used orally before tumor inoculation. This was quite a different characteristic from other similar preparations.

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Colony-forming efficiency of Ehrlich ascites tumor cells grown 7 days (plateau phase) in abdominal cavity of mice decreased immediately, then increased with time until 7hr after single exposure to Bleomycin. This finding indicates that Bleomycin induced a potentially lethal damage which could be repaired under in vivo condition.

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Slowing of the electrophoretic mobility of macrophages was observed as a result of lymphocyte sensitization by using peripheral lymphocytes from Donryu rats immune to Yoshida sarcoma and the soluble antigen of the same tumor. The slowing rate was found to be proportional to the number of lymphocytes used.

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CDF₁ mice were pretreated intrapertioneally with OK-432 and then leukemia P388 was inoculated intraperitoneally. On the day after tumor inoculation, cyclophosphamide was injected intraperitoneally and mice were again treated with OK-432. The best antitumor effect was seen in the combination of pre- and post-treatment with OK-432 and cyclophosphamide treatment.

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Oral administration of N-ethyl-N-(4-hydroxybutyl)nitrosoamine (EHBN) and its principal urinary metabolite, N-ethyl-N-(3-carboxypropyl)nitrosoamine (ECPN), selectively induced urinary bladder cancer in male ACI/N rats. It was demonstrated that EHBN as well as ECPN was more effective urinary bladder carcinogens in the rat than N-butyl-N-(4-hydroxybutyl) nitrosoamine.

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