Molecular dosimetry of DNA adducts in Chinese hamster ovary cells and C3H10T1/2 mouse embryo fibroblast cells treated with benzo[a]pyrene.
Chromatographic profiles of DNA adducts formed following treatment of Chinese hamster ovary (CHO) cells or C3H10T1/2 mouse embryo fibroblast cells with benzo[a]pyrene (BP), in the presence or absence of rat liver S9 fraction, have been obtained by both direct labelling ([3H]BP) and 32P-post-labelling methods. The principal adduct formed in both cell lines was (+)-N2-(7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene- 10S-yl) 2'-deoxyguanosine (detected as its 3',5'-bisphosphate by 32P-post-labelling). In both cell lines significantly higher levels of adducts were observed in the presence of S9 fraction. The results of these studies provide useful reference data on the genotoxic metabolism of BP in these widely used cell culture systems and allow comparisons with data obtained in other experimental mammalian systems. Valid comparisons of metabolism in experimental systems used as extrapolative models for man are particularly important where multiple bioactivation pathways are possible, such as in the case of polycyclic aromatic hydrocarbons.
Shell Research Ltd, Sittingbourne Research Centre, Kent, UK.
W P
WP
Watson
R J
RJ
Smith
D
D
Ryan
A L
AL
Meyer
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D004249:DNA Damage; D051379:Mice; D009154:Mutation; D051381:Rats
D018736:DNA Adducts; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D004247:DNA