A comparative study on mutagenesis of methylbenzylnitrosamine in V79 cells co-cultivated with liver or esophageal epithelial cells from chickens, rats and humans.
Cell-mediated activation of methylbenzylnitrosamine (MBN) to mutagenic metabolites was detected by the induction of forward gene mutation and sister chromatid exchange (SCE) in V79 cells co-cultivated with hepatocytes or esophageal epithelial cells from humans, rats or chickens. In the rat and chicken hepatocyte-mediated mutagenesis, a significant increase in SCE and 6-thioguanine resistant (6-TGr) mutants was noted in V79 cells exposed to MBN. The induction of 6-TGr mutant was also noted in V79 cells co-cultivated with human fetal hepatocytes, but the increase in SCE was trivial. In the assay of rat esophageal epithelial cell-mediated mutagenesis, MBN could be activated significantly to mutagenic metabolites to induce SCE and 6-TGr mutants in V79 cells, but this nitrosamine did not show any mutagenic action on V79 cells co-cultivated with chicken esophageal cells. No esophageal carcinoma was found in 26 Leghorn cocks treated with MBN for as long as 975 days, the largest total dose being 1674.86 mg. The experimental results show that chicken esophagus is probably not susceptible to the carcinogenic action of common volatile nitrosamines. At the present time, there is no evidence to indicate that the development of pharyngo-esophageal carcinoma in Linxian chickens was due to the volatile nitrosamines that occurred in the local foods. The human esophageal epithelial cells showed a certain ability to activate MBN to metabolites mutagenic to V79 cells, but this ability was much lower with human esophageal cell activation than with rat cells. Further studies are required to elucidate the importance of nitrosamines in the etiology of human esophageal carcinoma in the high-incidence areas.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002645:Chickens; D006224:Cricetinae; D003412:Cricetulus; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity; D004848:Epithelium / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008168:Lung; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013045:Species Specificity
D002273:Carcinogens; D009153:Mutagens; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine