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Covalent binding of dibenzpyrenes and benzo[a]Pyrene to DNA: evidence for synergistic and inhibitory interactions when applied in combination to mouse skin
Chester Beatty Laboratories, Institute of Cancer Research Fulham Road, London, SW3 6JB, UK
Several well-documented examples of human exposure to car cinogens involve complex mixtures of polycydlic aromatic hydrocarbons (PAHs). Although the biological properties of many pure PANs have been Investigated, less is known about their effects when present as components of mixtures. As the ability to form DNA adducts in vivo Is generally indicative of carcinogenic activity of PAHs, we have compared the DNA binding potencles of dibenzo[a,e]pyrene (DB[a,e]P), dibenzo[a,h]pyrene (DB[a,h]P), dibenzo[a,i]pyrene (DB[a,i]P),dibenzo[a,l]pyrene (DB[a,l]P) and benzo [a]pyrene (B[a]P), when applied topically, either singly or in combination, to the skin of male Parkes mice. DNA isolated from the skin and lungs was analysed by 32P-postlabelling. The adducts formed by each PAM exhibited markedly different chromato graphic mobifities on polyethylenelmine-cellulose TLC plates. The relative binding potendies of the compounds in both skin and lungs were: DB[a,l]P> B[a]PDB > DB[a,h]P > DB[a,i]P > DB[a,e]P, in good agreement with their reported carcinogenicitlesin mouse skin. The majority of adducts were removed from DNA within 21 days of treat ment, but low levels of adducts were found to persist for at least 3 months in both tissues. When DB[a,l]P, DB[a,e]P and B[a]P were applied together to mouse skin, a total binding 31% lower than expected was detected, while with a mixture of DB[a,e]P and B[a]P the binding to DNA In skin was 65% higher than expected from the binding Levels of the carcino gens when applied singly. Other binary combinations of these three PAils gave adduct levels similar to the sum of the binding levels of the individual components when applied singly. The results demonstrate the usefulness of 32 labelling for the assessment of the DNA binding potencies of PAHs in mouse tissues, and for the detection of interactions between components of mixtures of carcinogens.
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