Pyridine does not induce unscheduled DNA synthesis (UDS) in hepatocytes ofmale B6C3F1 mice treated in vivo

Pyridine was evaluated in an in vivo/in vitro mouse DNA repair assay. Unsch eduled DNA synthesis (UDS) was used as an indicator of DNA damage to hepato cytes from male B6C3F1 mice. Test animals were exposed by oral gavage to py ridine or to the vehicle or positive control articles, and hepatocytes were collected and labeled by incubation in media supplemented with [H-3]thymid ine. Following labeling, the cultures were processed for autoradiographic a nalysis. Doses were selected based on a pilot study in which 0, 250, 500, 7 50, 1000 or 2000 mg kg(-1) pyridine in water was administered by gavage, Mi ce in the 1000 and 2000 mg kg(-1) dose groups were comatose following dosin g and died within 24 h of dose administration. Pyridine dose levels for the UDS determination were set at 175, 350 and 700 mg kg(-1). Pyridine solutio ns in water were administered to mice 2 or 16 h prior to the scheduled sacr ifice. The vehicle control group received water 16 h before sacrifice and t he positive control group received 10 mg kg(-1) dimethylnitrosamine (DMN) 2 h before sacrifice. Pyridine did not significantly increase the UDS respon se in hepatocytes isolated from the treated animals, as measured by the inc orporation of [H-3]thymidine, using standard criteria for a negative respon se: less than zero mean net grains in repair (NG) and <20% of cells in repa ir (% IR; cells in repair have at least 5 NG), The vehicle control group an d the low, mid- and high pyridine dose groups yielded less than -8.3 NG and <less than or equal to>1% IR, The positive control group yielded a positiv e UDS response, with 10.8 NG and 62% IR, These results indicate that pyridi ne is non-genotoxic in B6C3F1 mouse liver using the UDS endpoint, Copyright (C) 2000 John Whey & Sons, Ltd.