Editors Highlight: Interactive Genotoxicity Induced by Environmentally Relevant Concentrations of Benzo(a)Pyrene Metabolites and Arsenite in Mouse Thymus Cells

Arsenic and polycyclic aromatic hydrocarbon (PAH) exposures affect many people worldwide leading to cancer and other diseases. Arsenite (As+3) and certain PAHs are known to cause genotoxicity. However, there is limited information on the interactions between As+3 and PAHs at environmentally relevant concentrations. The thymus is the primary immune organ for T cell development in mammals. Our previous studies showed that environmentally relevant concentrations of As+3 induce genotoxicity in mouse thymus cells through Poly(ADP-ribose) polymerase (PARP) inhibition. Certain PAHs, such as the metabolites of benzo(a)pyrene (BaP), are known to cause DNA damage by forming DNA adducts. In the present study, primary mouse thymus cells were examined for DNA damage following 18 hr in vitro treatments with 5 or 50 nM As+3 and 100 nM BaP, benzo[a]pyrene-7,8-dihydrodiol (BP-Diol), or benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). An interactive increase in genotoxicity and apoptosis were observed following treatments with 5 nM As + 3 + 100 nM BP-diol and 50 nM As + 3 + 100 nM BPDE. We attribute the increase in DNA damage to inhibition of PARP inhibition leading to decreased DNA repair. To further support this hypothesis, we found that a PARP inhibitor, 3,4-dihydro-5[4-(1-piperindinyl) butoxyl]-1(2H)-isoquinoline (DPQ), also interacted with BP-diol to produce an increase in DNA damage. Interestingly, we also found that As+3 and BP-diol increased CYP1A1 and CYP1B1 expression, suggesting ...

Source: Toxicological Sciences - October 27, 2016 Category: Toxicology Authors: Xu, H., Lauer, F. T., Liu, K. J., Hudson, L. G., Burchiel, S. W. Tags: Genotoxicity of Benzo(a)pyrene and Arsenite Source Type: research