Abstract
Phosphorylation of histon H2AX (termed g-H2AX) was recently identified as an early event after induction of DNA double strand breaks (DSBs). g-H2AX induced by ionizing radiation and anti-cancer drugs, forms nuclear foci that are microscopically visible by immunofluorescence staining. We have previously shown that coexposure to benzo(a)pyrene (BaP), a wide-spread environmental carcinogen, and ultraviolet A (UVA), a major component of solar UV radiation, induced DSBs in mammalian cells. In present study, we examined whether coexposure to BaP and UVA induces g-H2AX in CHO-K1 cells. Single treatment with BaP (10-9-10-7) or UVA (~2.4J/cm2) did not induce g-H2AX, however, coexposure drastically induced foci of g-H2AX in dose-dependent manner. Furthermore, the induction of g-H2AX by coexposure was efficiently inhibited in the presence of NaN3, indicating that induction was due to the production of singlet oxygen. This is the first visual evidence that coexposure to BaP and UVA, a one of the environmental combined pollution, induced DSBs, involving g-H2AX. Interestingly, we successfully detected the g-H2AX at very low concentration of BaP, which did not change the cell survival rates. Epigenetic change is recently considered to relate with cancer initiation. DSBs and accompanied g-H2AX might contribute to photocarcinogenesis of environmental concentration of polycyclic aromatic hydrocarbons.
