Pyridine does not induce unscheduled DNA synthesis (UDS) in hepatocytes of male B6C3F1 mice treated in vivo.
Pyridine was evaluated in an in vivo/in vitro mouse DNA repair assay. Unscheduled DNA synthesis (UDS) was used as an indicator of DNA damage to hepatocytes from male B6C3F1 mice. Test animals were exposed by oral gavage to pyridine or to the vehicle or positive control articles, and hepatocytes were collected and labeled by incubation in media supplemented with [3H]thymidine. Following labeling, the cultures were processed for autoradiographic analysis. Doses were selected based on a pilot study in which 0, 250, 500, 750, 1000 or 2000 mg kg(-1) pyridine in water was administered by gavage. Mice in the 1000 and 2000 mg kg(-1) dose groups were comatose following dosing 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 solutions in water were administered to mice 2 or 16 h prior to the scheduled sacrifice. The vehicle control group received water 16 h before sacrifice and the positive control group received 10 mg kg(-1) dimethylnitrosamine (DMN) 2 h before sacrifice. Pyridine did not significantly increase the UDS response in hepatocytes isolated from the treated animals, as measured by the incorporation of [3H]thymidine, using standard criteria for a negative response: less than zero mean net grains in repair (NG) and <20% of cells in repair (% IR; cells in repair have at least 5 NG). The vehicle control group and the low, mid- and high pyridine dose groups yielded less than -8.3 NG and < or =1% IR. The positive control group yielded a positive UDS response, with 10.8 NG and 62% IR. These results indicate that pyridine is non-genotoxic in B6C3F1 mouse liver using the UDS endpoint.
MacGregor
J A
JA
Toxicology Consulting Services, Rockville, MD 20852, USA. jmacgregor@erols.com
Hamilton
C M
CM
Kubicek
J E
JE
Mirsalis
J C
JC
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D004260:DNA Repair / Q000187:drug effects*; D004128:Dimethylnitrosamine / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011725:Pyridines / Q000494:pharmacology*
D002273:Carcinogens; D011725:Pyridines; D004128:Dimethylnitrosamine; C023666:pyridine