Modulation of the in vivo covalent binding of the carcinogen benzo(a)pyrene to rat liver DNA by selective induction of microsomal and nuclear aryl hydrocarbon hydroxylase activity.
The influence of microsomal (mAHH) and nuclear (nAHH) aryl hydrocarbon hydroxylase activity on the covalent binding of tritiated benzo(a)pyrene to rat liver DNA was evaluated in vivo. Induction of mAHH was obtained after phenobarbitone treatment (180% of control), which increased DNA binding to 210%, but left the nAHH unchanged. mAHH and nAHH were slightly induced with dieldrin (130% and 120%), but the binding remained unchanged. The increasing effect of mAHH as well as the possibly decreasing effect of nAHH induction on the binding became obvious when the data of 11 individual rats were used to solve the equation Binding = aX(mAHH) + bX(nAHH) + c. Multiple linear regression analysis resulted in positive values for a and c, a negative value for b, and a multiple correlation coefficient R = 0.82. An influence of other enzymes involved in the metabolism of benzo(a)pyrene cannot be excluded. The study shows clearly that the binding of a foreign compound to DNA in vivo is not only dependent on microsomal enzyme activities but also on nuclear activities even if the latter are considerably lower than those of microsomes.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism*; D001580:Benzopyrenes / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology; D004247:DNA / Q000378:metabolism*; D004026:Dieldrin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D001580:Benzopyrenes; D004247:DNA; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D004026:Dieldrin; D010634:Phenobarbital