Microsome-mediated clastogenicity of butylated hydroxyanisole (BHA) in cultured Chinese hamster ovary cells: the possible role of reactive oxygen species.
Butylated hydroxyanisole (BHA) was found to induce chromosome aberrations in Chinese hamster ovary (CHO) cells in the presence of Aroclor-induced rat-liver S9. The effects were more marked when washed microsomes were employed and chromosome damage was considerably reduced in the presence of catalase, suggesting that hydrogen peroxide was involved. Stimulation of H2O2 production by BHA in S9 or microsome incubation mixtures was demonstrated using the catalase-mediated production of formaldehyde from methanol. One of the major microsomal metabolites of BHA, tert.-butyl hydroquinone (t-BHQ), which autoxidises in solution producing H2O2 also induced extensive catalase-sensitive chromosome damage in the absence of metabolic activation. These observations suggest that extracellular generation of reactive oxygen species may be implicated in the mechanism of BHA clastogenicity in vitro. However, chromosome damage was not completely abolished by catalase and the end product of t-BHQ oxidation, tert.-butyl quinone, was also weakly clastogenic, suggesting that intracellular effects of quinone metabolites may also be involved in the clastogenicity of BHA.
Phillips
B J
BJ
BIBRA, Carshalton Surrey, Great Britain.
Carroll
P A
PA
Tee
A C
AC
Anderson
D
D
D000818:Animals; D001711:Biotransformation; D002083:Butylated Hydroxyanisole / Q000493:pharmacokinetics / Q000633:toxicity*; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D002869:Chromosome Aberrations / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D006861:Hydrogen Peroxide / Q000378:metabolism; D006873:Hydroquinones / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D008861:Microsomes / Q000187:drug effects* / Q000378:metabolism; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains
D006873:Hydroquinones; D002083:Butylated Hydroxyanisole; D006861:Hydrogen Peroxide; C018855:2-tert-butylhydroquinone; D002374:Catalase