The carcinogenicity of tar-containing skin drugs, Pityrol, Glyteer, Ichthammol JP. pine tar JP, and Metashal, was investigated by animal experiments and by chemical analysis of carcinogenic aromatic hydrocarbons. The results of animal experiments showed that the proportions of skin papilloma-bearing mice as compared to those at the first appearance of tumor were 64% (Pityrol), 71% (Glyteer), 9% (Ichthammol), 23% (pine tar), and 64% (Metashal). The proportions of skin carcinoma-bearing mice were 36% (Pityrol), 40% (Glyteer), 0% (Ichthammol), 6% (pine tar), and 22% (Metashal). A high proportion (37%) of metastasis in adjacent or remote organs was observed. No tumors developed in the control group that received acetone only.
As for chemical analysis, a substantial amount of polycyclic aromatic hydrocarbons and, in particular, of benzo[a]pyrene was identified. The content of benzo[a]-pyrene agreed well with the degree of carcinogenic activity observed by the animal experiment. The average amount of benzo[a]pyrene, from three measurements, were 145 (Pityrol), 129 (Glyteer), none (Ichthammol), 48 (pine tar), and 80μg/10g (Metashal).
The carcinogenicity of these drugs in man is difficult to assess at present and further epidemiologic studies appear to be needed to clarify this point.

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Male Wistar rats and male BALB/c mice received 0.05% N-butyl-N-(4-hydroxybutyl) nitrosoamine (BBN) solution as drinking water. After more than 10 weeks, 8 hyperplasias of the epithelium, 5 papillomas, and 36 carcinomas developed selectively in the bladder were found in 49 of the rats, while 4 hyperplasias, 3 papillomas, and 36 carcinomas of the bladder were found in 43 of the mice, After more than 25 weeks, all the rats and mice examined had developed tumors including 3 papillomas in the bladder. The mean induction time of carcinomas was 55.1 weeks in rats and 30.7 weeks in mice, All carcinomas induced in rats were papillary, and histologically they were transitional cell (83.3%) or squamous cell (16.7%) type. About 2/3 of the tumors showed no invasion into the bladder wall. Carcinomas of mice were squamous cell (52.8%), transitional cell (38.9%), or anaplastic (8.3%) type, and all were more or less invasive. No metastatic foci were found in rats or mice.

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The membrane-active agents, Polymyxin-B and Amphotericin-B, potentiated the action of fusidic acid on protein synthesis, and secondarily on RNA synthesis in the cultured fibroblastic cell line, RFL, and its transformant, RFL-T. In addition, some release of RNA and protein from the cells was observed after treatment with the two membrane-active agents employed and increased in parallel with the doses, especially at a high dosage.

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Based on a lipid-absorbing ability of lymphatic capillaries, fat emulsion method was applied to deliver more increasing amount of water-soluble anticancer agents selectively into regional lymph nodes.
After intratesticular injection of various types of emulsions in rats, emulsion droplets selectively reached regional lymph nodes in 15min and remained there for more than seven days. A comparison of radioactivity in regional lymph nodes after intratesticular injections of various types of preparations containing labeled anticancer agent, ³H-5-fluorouracils, howed that the highest value was a water-in-oil-in-water (W/O/W) emulsion, followed by a water-in-oil (W/O) and an oil-in-water (O/W) emulsion, and aqueous solution. All values were higher than after intravenous injection of an aqueous solution. Intratesticular injection of W/O emulsion resulted in a value 2.7 times higher than intratesticular injection of aqueous solution and 3.1 times higher than intravenous injection of aqueous solution. The corresponding values for W/O/W emulsion were 7.9 and 9.1.

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The rôle of lymphoid cells in the antitumor activity of a polysaccharide, lentinan, has been analyzed.
1) The antitumor effect of lentinan is produced in the host at an early date, within 2-4 days after tumor transplantation, and X-irradiation after that period does not reduce the antitumor activity of lentinan. (2) During the regression of tumor by administration of lentinan, the peritoneal cells that inhibit the growth of tumor appear already in the peritoneal fluid 4-7 days after transplantation, and after 30 days when the tumor has completely regressed, cytotoxicity of peritoneal cells increases markedly. (3) Lentinan itself has the effect of activating the antitumor effect of peritoneal exudate cells against sarcoma-180, within 7 days after the last administration of lentinan. (4) Passive transfer of the antitumor activity can be achieved with the peritoneal cells, but not with lymph node cells or serum.

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Type IV hexokinase, also called glucokinase from the liver of the Morris hepatomabearing rat, often splits into two components on electrophoresis, one moving fast (IV_f) and the other slowly (IV_s). Type IV hexokinase, commonly seen in the normal rat liver, coincided with type IV_s but that found in the Morris hepatoma tissues was identified as type IV_f by its position on electrophoresis. The mechanism of splitting of type IV hexokinase and its nature are discussed.

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4-(Dimethylamino) azobenzene (DAB) carcinogenesis in rats was delayed by the simultaneous administration of phenobarbital, but accelerated by DL-ethionine. The present investigation deals with the relationship between the primary metabolisms of DAB in the liver, the cytochrome P-450 content in liver microsomes, and the carcinogenesis in rats receiving DAB alone or DAB plus DL-ethionine or phenobarbital. DAB administration had no marked influence on DAB-metabolizing enzymes as well as P-450 content throughout the precancerous period. DAB plus phenobarbital administration promoted activities of the oxidative metabolizing enzyme and P-450 content. In contrast, DAB plus DL-ethionine treatment markedly depressed the hepatic activity to N-demethylate DAB without giving a marked influence on other enzymes during the long period of administration.

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Autoradiographic and biochemical studies on DNA synthesis and histochemical studies of leucine aminopeptidase and alkaline phosphatase were performed on the glandular stomach of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). A solution of 167μg/ml of MNNG in deionized water was administered freely to 60 male Wistar strain rats as drinking water and the rats were examined at intervals for about 70 weeks. One hour before sacrifice, rats were injected with ³H-thymidine intraperitoneally and their tissues were examined by autoradiography and biochemical analysis. Three morphological types of lesions of the stomach were distinguished with different distribution and percentage of labeled cells. The labeling indices of regenerative glandular hyperplasia, upward or downward adenomatous hyperplasia, and adenocarcinoma were 14.0±2.7, 8.3±1.4, or 10.4±3.3 and 11.1±2.6%, respectively. The rate of DNA synthesis in the whole stomach decreased in the 1st stage of carcinogenesis (during the first 20 weeks), increased in the 2nd stage (from the 20th to 30th week), and again decreased in the 3rd stage (after the 30th week). Leucine aminopeptidase and alkaline phosphatase activities were observed only in the stroma of the adenocarcinoma. The high rates of DNA synthesis in regenerative glandular hyperplasia and precancerous stomach are discussed.

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The receptor sites for Ricinus communis agglutinin (ricin) in two non-malignant cell lines, clone 1-82 and clone M6, and of their parent line of cultured mouse mammary tumor cells, FM3A/B, were studied with ¹²⁵I-labeled or fluorescent ricin. The nonmalignant cells showed increased agglutinability, and the amount of ricin bound to them was about 1.4 times more than that bound to the malignant parent tumor cells. However, the amount of ricin bound to non-malignant cells per unit surface area was similar to that bound to the malignant cells since they had a larger surface area than the malignant cells. The possibility of a difference in the topological distribution of the receptor sites of ricin on malignant and non-malignant cells, rather than a difference in the number of receptor sites, was discussed in connection with the increased agglutinability of the non-malignant cells.

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Antitumor activity of the newly synthesized haloacetyl derivalives of carbazole, phenoxsazine, acridine, oriminodibenzyl was examined on ascites sarcoma-180. lodoacetylcarbazole was the most active and its therapeutic index was 26. Carbazole ring and bromocr iodo-acetyl groups were suitable for the antitumor activity among the ring systems and side chains.

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Multiple intravenous injections of 7, 12-dimethylbenz[a]anthracene in the rat induced a sustained reduction of immunocompetent cells in the spleen, while single injection caused a temporary reduction. From these results, it is possible that multiple injections play a rôle in leukemogenesis with multiple intravenous doses of this compounds.

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Estradiol binding capacities of the DMBA-induced mammary tumors in 8 rats were measured by an in vitro method using dextran-coated activated charcoal. Its results suggested that higher capacities were found in tumors better responding to oophorectomy, and lower capacities in more autonomous tumors.

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In spontaneous mammary tumors in mice, the following six measures were highly correlated to each other, except DNA/mg dry weight, indicating the validity of applying these measures even to necrotic tumors; arithmetical or geometrical mean of the major two diameters, wet dry weight, total DNA, and DNA/mg dry weight.

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The characteristic patterns of two human epithelial cell lines were demonstrated by observing the shape, number size, and internal structure of their cell aggregates cultured in gyrating flasks, and those of the tumors produced through transplantation into the peritoneal cavity of immunosuppressed hamsters.

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The autoradiographic study was made on the effect of urinary tryptophan metabolites on the bladder epithelium of rats and its results indicated that a large amount of tryptophan metabolites may stimulate DNA synthesis in the epithelial cells of the bladder.

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1, 1'-Ethylenebis(1-nitrosourea) and 1, 1'-hexamethylenebis(1-nitrosourea) showed marked inhibitory effects on the growth of AH-13 and L-1210 cells, in vivo. Cytological effects of these compounds on the AH-13 cells were similar to those of alkylating agents. Survival time of the hosts was prolonged up to 200-300% by their repeated intraperitoneal injections.

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