Benzo(a)pyrene represses melanogenesis in B16F10 mouse melanoma cells

Abstract

Benzo(a)pyrene (BaP) is a chemically based polycyclic aromatic hydrocarbon (PAH) that is readily absorbed by the skin. BaP is metabolized to BaP-diol-epoxide by cytochromes P-450 1A1/2 (CYP1A1/2) and cytochromes P-450 1B1 (CYP1B1) in the cytosol. BaP and its metabolites induce genotoxicity and cancer. Although BaP easily accumulates in melanin-containing tissues as well as other tissue types, the effects of BaP on melanocytes are not fully understood. Here, we show that 40-100 µM BaP represses melanin synthesis in B16F10 cells. The decrease of melanin contents is induced by tyrosinase activity in BaP-exposed B16F10. However, this repression of melanin synthesis is not induced by direct inhibition of tyrosinase in in vitro assay. Therefore, we show whether BaP regulated melanin synthesis-related enzyme. BaP regulates melanin synthesis by Tyr and Tyrpl expression. In addition, these genes expression is down-regulated by Mitf repressed by BaP. Importantly, the repression was provoked in the absence and presence of α-melanocyte stimulating hormone (α-MSH). Therefore, we hypothesize BaP interrupts the UV protection mechanism by repressing melanin synthesis in the skin. Taken together our results have revealed new side effects that exposure of BaP abolished melanin synthesis in melanocytes.