Cell replication and unscheduled DNA synthesis (UDS) activity of low molecular weight chlorinated paraffins in the rat liver in vivo.
The rodent carcinogen C12-chlorinated paraffin (C12-CP) has been evaluated for unscheduled DNA synthesis (UDS) activity in the rat liver in vivo. Evidence of cell proliferation was also assessed by measuring cells undergoing semi-conservative DNA activity (S phase). No evidence of UDS was observed at doses up to 2 g/kg at either 2 or 12 h after dosing. Concomitant positive UDS responses were observed for the liver genotoxins N-nitrosodimethylamine, 4-aminobiphenyl, methyl methanesulphonate, 2-acetylaminofluorene, benzidine and 6-dimethylaminophenylazobenzthiazole. A strong positive response was observed in the cell proliferation assay for the test agent and the positive control agents quinoline and 4-acetylaminofluorene. These observations are discussed within the context of the rodent carcinogenicity reported for the same sample of C12-CPs as studied by the US National Toxicology Program.
Ashby
J
J
ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Lefevre
P A
PA
Elcombe
C R
CR
D000818:Animals; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007399:Interphase / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D010232:Paraffin / Q000633:toxicity*; D051381:Rats
D002273:Carcinogens; D006843:Hydrocarbons, Chlorinated; C010555:chlorowax 500C; D010232:Paraffin; D004247:DNA