Abstract
CHEMICAL carcinogens, for example, benzo[a]pyrene (BaP), are metabolised to reactive intermediates which bind covalently to cellular macromolecules1–3 and the extent of binding seems to correlate with the carcinogenic potency of the hydrocarbons1. Through various mutagenicity, metabolism and binding studies, the intermediate which undergoes formation of a stable covalent complex with DNA has been identified as 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene (BaP diol epoxide)4–9. The structure of a covalent adduct formed between this hydrocarbon and poly(G) has also been established6–9. We report here the identity of several adducts obtained by reacting (±)BaP diol epoxide with tritium-labelled DNA. Four differently labelled lots of DNA were synthesised in vitro with DNA polymerase I by incorporating in each case three unlabelled and one tritium labelled nucleoside triphosphate. Through the use of this unambiguous labelling technique we have demonstrated that activated BaP forms two adducts with deoxyguanosine, two with deoxyadenosine and possibly one wtih deoxycytidine, while reaction with deoxy-thymidine was not detected. This approach also allowed the relative percentage of each adduct to be calculated. The deoxyguanosine adducts predominated and constituted 92% of the total stable covalent adducts formed.
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