A general Mechanistic Model of Bromate Cytotoxicity Mediated by DNA Damage | ||
| Egyptian Academic Journal of Biological Sciences, F. Toxicology & Pest Control | ||
| Article 6, Volume 10, Issue 2, December 2018, Pages 69-79 PDF (757.02 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/eajbsf.2018.22728 | ||
| Authors | ||
| Mahmoud I. Shoulkamy1; Hiroshi Ide2 | ||
| 1Department of Zoology, Faculty of Science, Minia University, Minia 61519, Egypt | ||
| 2Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526, Japan | ||
| Abstract | ||
| Potassium bromide (KBrO3) is widely used in bread production, cosmetics and water disinfection. KBrO3 is a DNA oxidizing agent that induces base modifications as 8-Oxo-deoxyguanosine (8-oxodG), also induces chromosomal aberrations, micronuclei and γH2AX foci which are the endpoints of DNA double-strand breaks (DSBs). Therefore, the cytotoxic and genotoxic effects of KBrO3 are mainly related to DNA damage. Conversely, the role of DNA damage in the cytotoxic effects of KBrO3 has been poorly understood in conjunction with that of protein damage. Herein, we illustrated the cytotoxic effects of KBrO3 through DNA damage-dependent and DNA damage-independent mechanisms. For this proof of concept, we analyzed the sensitivity of DNA repair-proficient and –deficient cells and subsequently measure DNA and protein damage after treatment with KBrO3. Our results show that the DNA repair genes DNA-PKcs, XRCC3 and RAD51D are strongly required for cell survival and essential to alleviate the cytotoxic effect of KBrO3. The quantitative analysis of DSBs upon treatment with KBrO3 shows a significant increase in the yields of DSBs suggesting that DSBs are critical DNA damage induced by KBrO3 and accounts for DNA damage-dependent cytotoxicity. Furthermore, thioredoxin 1 oxidation was not observed upon treatment with potassium bromide, strongly exclude the involvement of DNA damage-independent cytotoxicity based on protein damage. Based on the current findings we suggested a mechanistic model of bromate cytotoxicity that is mediated by DNA but not protein damage. | ||
| Keywords | ||
| Potassium bromide; Cytotoxicity; DNA damage; DNA repair; Oxidizing agent; Protein damage | ||
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