Human exposure to polycyclic aromatic hydrocarbons (PAHs) occurs through complex mixtures. The National Institute of Standards and Technology has established standard reference materials (SRMs) for selected PAH mixtures that are composed of carcinogenic, noncarcinogenic, and weakly carcinogenic compounds, such as those derived from coal tar (SRM 1597), atmospheric particulate matter (SRM 1649), and diesel particulate matter (SRM 1650). To study the effects of PAHs with different carcinogenic potential in complex mixtures, and to investigate the metabolic activation of noncarcinogenic and weakly carcinogenic PAHs to DNA-binding derivatives, artificial mixtures (1597H, 1649H, and 1650H) were prepared in the laboratory. These artificial mixtures contained the same relative ratios of noncarcinogenic and weakly carcinogenic PAHs present in SRM 1597, SRM 1649, and SRM 1650. The human mammary carcinoma-derived cell line MCF-7 was treated with these artificial mixtures and analyzed for PAH-DNA adduct formation and the induction of cytochrome P450 (CYP) enzymes. We found that the artificial mixtures formed lower but detectable levels of DNA adducts 24 and 48 hr after treatment than benzo[a]pyrene. Induction of CYP enzyme activity was measured by the ethoxyresorufin-O- deethylase assay, and the expression of CYP1A1 and CYP1B1 was confirmed by immunoblots. Both noncarcinogenic and weakly carcinogenic PAHs present in the artificial mixtures have the ability to induce CYP1A1 and CYP1B1 in MCF-7 cells and contribute to DNA binding. Therefore, it is necessary to take into account the noncarcinogenic and weakly carcinogenic PAHs present in environmental mixtures in assessing the potential risk associated with human exposure.
All Science Journal Classification (ASJC) codes
- Health, Toxicology and Mutagenesis