Benzo[a]pyrene differentially alters mitochondrial and nuclear DNA synthesis in primary hepatocyte cultures.

The incubation of non-proliferating primary cultures of rat hepatocytes with benzo[a]Pyrene for 24 or 48 hours produced a concentration-dependent stimulation of nuclear DNA synthesis (measured as [3H]thymidine incorporation into isolated, purified DNA) whereas the normal processes of D-loop formation and expansion synthesis on mitochondrial DNA were inhibited by as much as 62% of that in control cells. Incubation of cultures with [3H]benzo[a]pyrene showed that highly purified mitochondrial DNA retained 4-15 times more covalently bound adducts per unit length of DNA than did nuclear DNA. We suggest, therefore, that this carcinogenic, environmental pollutant may exert its most profound effects on the mitochondrial, rather than the nuclear, genetic apparatus.