Mitochondrial DNA is a major cellular target for a dihydrodiol-epoxide derivative of benzo[a]pyrene

Abstract

When mammalian cell cultures are exposed for 2 hours to (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, a mutagenic and carcinogenic derivative of benzo[a]pyrene, the extent of covalent modificationof mitochondrial DNA is 40 to 90 times greater than that of nuclear DNA. Evidence is presented that this reflects the lipophilic character of the derivative and the very high ratio of lipid to DNA in mitochondria. These results suggest that mitochondrial DNA may be an important cellular target of chemical carcinogens.