Hepatocyte-mediated production of sister chromatid exchange in co-cultured cells by acrylonitrile: evidence for extra cellular transport of a stable reactive intermediate.
To study the possibility that liver metabolism of acrylonitrile (ACN) could produce a stable carcinogenic metabolite that causes the brain tumors produced by ACN, the ability of hepatocytes to generate a stable transportable mutagenic metabolite in culture was studied. ACN did not produce sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells, but a significant increase was produced when CHO cells were co-cultured with freshly isolated rat hepatocytes. Induction of SCE in CHO cells co-cultured with hepatocytes suggests that the liver cells metabolize ACN and the reactive metabolite is transported from them to the CHO cells.
D000181:Acrylonitrile / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D005260:Female; D008099:Liver / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D010053:Ovary; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D009570:Nitriles; D000181:Acrylonitrile