Investigation of mechanism(s) of DNA damage induced by 4-monochlorobiphenyl (PCB3) metabolites.

Environment International
Wei XieG Ludewig

Abstract

4-Monochlorobiphenyl (PCB3) is readily converted by xenobiotic-metabolizing enzymes to dihydroxy-metabolites and quinones. The PCB3 hydroquinone (PCB3-HQ; 2-(4'-chlorophenyl)-1,4-hydroquinone) induces chromosome loss in Chinese Hamster V79 cells, whereas the para-quinone (PCB3-pQ; 2-(4'-chlorophenyl)-1,4-benzoquinone) very efficiently induces gene mutations and chromosome breaks. Apparently, each of these two metabolites, which are a redox pair, has a different spectrum of genotoxic effects due to different, metabolite-specific mechanisms. We hypothesized that the HQ requires enzymatic activation by peroxidases with the formation of reactive oxygen species (ROS) as the ultimate genotoxin, whereas the pQ reacts directly with nucleophilic sites in DNA and/or proteins. To examine this hypothesis, we employed two cell lines with different myeloperoxidase (MPO) activities, MPO-rich HL-60 and MPO-deficient Jurkat cells, and measured cytotoxicity, DNA damage (COMET assay), MPO activity, intracellular levels of reactive oxygen species (ROS) and intracellular free -SH groups (monochlorobimane assay, MCB) and free GSH contents (enzyme recycling method) after treatment with PCB3-HQ and PCB3-pQ. We also examined the modulation of these eff...Continue Reading

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Citations

Dec 6, 2012·Cancer Letters·Gabriele Ludewig, Larry W Robertson
Aug 8, 2013·Molecular Cancer·Enas A El-KarimVincent W Yang
Jan 30, 2015·Critical Reviews in Toxicology·Fabian A GrimmLarry W Robertson
Nov 26, 2015·Atmospheric Environment·Andres MartinezKeri C Hornbuckle
Mar 31, 2015·Reviews on Environmental Health·David O Carpenter
Jul 27, 2017·Environmental Science and Pollution Research International·Kiran DhakalLarry W Robertson

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