Title: Homologous recombination repair signaling in chemical carcinogenesis: prolonged particulate hexavalent chromium exposure suppresses the Rad51 response in human lung cells.
Authors: Qin, Qin; Xie, Hong; Wise, Sandra S; Browning, Cynthia L; Thompson, Kelsey N; Holmes, Amie L; Wise Sr, John Pierce
Published In Toxicol Sci, (2014 Nov)
Abstract: The aim of this study was to focus on hexavalent chromium, [Cr(VI)], a chemical carcinogen and major public health concern, and consider its ability to impact DNA double strand break repair. We further focused on particulate Cr(VI), because it is the more potent carcinogenic form of Cr(VI). DNA double strand break repair serves to protect cells against the detrimental effects of DNA double strand breaks. For particulate Cr(VI), data show DNA double strand break repair must be overcome for neoplastic transformation to occur. Acute Cr(VI) exposures reveal a robust DNA double strand break repair response, however, longer exposures have not been considered. Using the comet assay, we found longer exposures to particulate zinc chromate induced concentration-dependent increases in DNA double strand breaks indicating breaks were occurring throughout the exposure time. Acute (24 h) exposure induced DNA double strand break repair signaling by inducing Mre11 foci formation, ATM phosphorylation and phosphorylated ATM foci formation, Rad51 protein levels and Rad51 foci formation. However, longer exposures reduced the Rad51 response. These data indicate a major chemical carcinogen can simultaneously induce DNA double strand breaks and alter their repair and describe a new and important aspect of the carcinogenic mechanism for Cr(VI).
PubMed ID: 25173789
MeSH Terms: Carcinogenesis/drug effects*; Carcinogenesis/genetics; Carcinogens/toxicity*; Cell Culture Techniques; Cell Line; Chromates/toxicity*; Chromosome Aberrations/chemically induced; Comet Assay; DNA Breaks, Double-Stranded*; Humans; Lung/drug effects*; Lung/metabolism; Lung/pathology; Mutagens/toxicity; Rad51 Recombinase/genetics*; Recombinational DNA Repair*; Time Factors; Zinc Compounds/toxicity*