concanavalin-a and Cocarcinogenesis

The effect of thymosin fraction 5 (TF5) on the promotion and progression phases of urinary tract carcinogenesis induced by consecutive administration of phenacetin and N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in NON/Shi mice was investigated. The study was carried out twice with a minor modification to the protocol in the second experiment. Fifty-seven male NON/Shi mice in experiment 1 and 100 mice in experiment 2 were each divided into four groups. Phenacetin was administered for 8 weeks in experiment 1 and 12 weeks in experiment 2, and subsequently BBN was given for 6 weeks in both cases, for total observation periods of 30 and 34 weeks, respectively. Sixty micrograms of TF5 per mouse was inoculated subcutaneously twice a week during (group 2) or after (group 3) BBN exposure, or both periods (group 4). Group 1 served as a control group without TF5 treatment. Histopathological examination revealed no effects on either induction of urinary tract carcinomas or distant metastasis from renal pelvic carcinomas in either experiment.

Topics: Animals; Butylhydroxybutylnitrosamine; Carcinogens; Cocarcinogenesis; Concanavalin A; Drug Interactions; Lymphocytes; Male; Mice; Mice, Inbred Strains; Phenacetin; Phytohemagglutinins; Spleen; Thymosin; Urologic Neoplasms

In order to investigate the possibility that the theory of two-stage carcinogenesis can be applied to neurogenic carcinogenesis, we analyzed the promoting effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the in vitro malignant transformation of fetal rat brain cells exposed in utero to ethylnitrosourea (ENU). Rat brain cells were transferred to a cultured system at 72 h after a single pulse of ENU (50 mg/kg body weight) to pregnant SD-JCL rats on the 18th day of gestation. The positive findings of glial fibrillary acidic protein and S-100 protein in primary cultured cells by the analysis of immunohistochemistry revealed the neuroglial origin of transformed cells. These cells were divided into 12 groups and were treated twice per week with or without TPA at concentrations from 0.1 to 50.0 ng/ml. From the results of cellular morphology, Concanavalin A agglutinability, colony forming capacity in semisolid soft agar, and tumorigenicity in vivo, malignant transformation of fetal rat brain cells appeared earlier in the ENU group treated with TPA than in the untreated ENU group. On the basis of these observations, it is suggested that TPA might be effective as a tumor promoter on ENU-induced neurogenic carcinogenesis.

Topics: Animals; Brain Neoplasms; Cell Aggregation; Cell Division; Cell Transformation, Neoplastic; Cells, Cultured; Cocarcinogenesis; Concanavalin A; Ethylnitrosourea; Female; Glial Fibrillary Acidic Protein; Maternal-Fetal Exchange; Neoplasm Transplantation; Neoplastic Stem Cells; Phorbols; Pregnancy; Rats; Tetradecanoylphorbol Acetate

The promoting effects of various chemicals and dietary constituents on bladder carcinogenesis were examined by means of a short-term assay, in which maintenance of concanavalin A agglutination of isolated rat bladder cells caused by a subcarcinogenic dose of N-butyl-N-(4-hydroxybutyl)nitrosamine was used as an indicator. Twenty-seven chemicals were examined as possible promoters. Positive results in this assay were consistent with established promoting effects in the cases of sodium saccharin, saccharin, sodium L-ascorbate, sodium cyclamate, DL-tryptophan, butylated hydroxyanisole, butylated hydroxytoluene, L-thioproline and phenacetin. Allopurinol was the only established promoter that gave negative results in the agglutination assay. Thus, this method is useful for rapid evaluation of the specific promoting effect of a chemical on bladder carcinogenesis.

Topics: Agglutination Tests; Animals; Butylhydroxybutylnitrosamine; Carcinogens; Cocarcinogenesis; Concanavalin A; Drug Evaluation, Preclinical; In Vitro Techniques; Male; Rats; Rats, Inbred F344; Urinary Bladder Neoplasms

The effects of amino acids on the enhanced agglutinability of bladder cells with concanavalin A induced by subcarcinogenic treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine were examined. The amino acids examined were L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamic acid, L-glutamine, L-glycine, DL- and L-histidine, L-hydroxyproline, L-isoleucine, D- and L-leucine, L-lysine, L-methionine, DL- and L-phenylalanine, L-proline, L-serine, L-threonine, DL-, D- and L-tryptophan, L-tyrosine and D- and L-valine. They were added to powdered diet at a concentration of 2.0%. L-Leucine, L-isoleucine, L-valine, DL- and D-tryptophan prolonged the period during which the bladder cells showed enhanced agglutinability with concanavalin A. Leupeptin, a protease inhibitor, and L-leucyl-L-leucine were also examined at a concentration of 0.1% because of their similar chemical structures, and were found to have the same effect. The tumor-promoting effects of DL-tryptophan and leupeptin have already been established by in vivo carcinogenesis experiments. The effects of L-leucine, L-isoleucine, L-valine, D-tryptophan and L-leucyl-L-leucine, detected by this short term assay, suggest that these compounds may also be promoters of bladder cancer in rats.

Topics: Amino Acids; Animals; Butylhydroxybutylnitrosamine; Cell Aggregation; Cocarcinogenesis; Concanavalin A; Male; Rats; Rats, Inbred Strains; Urinary Bladder; Urinary Bladder Neoplasms

Saccharin is known to have a tumor-promoting effect on bladder cancer in rats, but its mechanism of action is unknown. We demonstrated that the increased agglutinability of isolated epithelial cells of the bladder in the presence of concanavalin A caused by a subcarcinogenic dose of bladder carcinogens disappeared shortly after the end of their administration. However, saccharin maintained the increased agglutinability when given continuously after administration of carcinogen. Moreover, the agglutinability of bladder cells previously exposed to a subcarcinogenic dose of bladder carcinogens increased again when saccharin was given after the agglutinability had disappeared completely.

Topics: Animals; Butylhydroxybutylnitrosamine; Cell Aggregation; Cell Membrane; Cocarcinogenesis; Concanavalin A; Diet; FANFT; Male; Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred Strains; Saccharin; Urinary Bladder; Urinary Bladder Neoplasms

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenoviruses, Human; Animals; Benzopyrenes; Cell Aggregation; Cell Division; Cell Transformation, Neoplastic; Cell Transformation, Viral; Clone Cells; Cocarcinogenesis; Concanavalin A; Embryo, Mammalian; Membrane Proteins; Phenotype; Phorbols; Plasminogen Activators; Rats; Tetradecanoylphorbol Acetate