DNA damage mediated by 4,4'-methylenebis(2-chloroaniline) cannot be detected via the DNA damage marker γH2AX: A case study
نویسندگان
چکیده
DNA damage may be induced by both intrinsic and extrinsic factors, the latter involving chemical exposure at workplaces. Upon induction, checkpoint kinases such as ATM ATR, phosphorylate serine 139 of histone H2AX generating γH2AX, to initiate response pathway. This allows antibodies that act against post-translational modifications, used for detecting genotoxicity. The aromatic amine 4,4'-methylenebis(2-chloroaniline) (MOCA), which is utilized in industry produce polyurethane resins, exhibits genotoxicity induces cancers animals, including rodents humans. damage, due MOCA-induced toxicity during its metabolism, believed first step towards carcinogenesis. However, we failed detect γH2AX induction MOCA cellular systems via western blotting, even when electrophoresis-based methods clearly indicated physical had been induced. In present study, RNA sequencing MOCA-treated cells controls elucidate factors underlying discrepancies observed between these two analytical systems. Our results mRNA expression was significantly downregulated; this finding partially clarified inefficient γH2AX. Although downregulation presence witnessed study quite unexpected, believe prompts researchers cautious screening using only, possibility being overlooked some cases. Thus, it appears a combined approach more suitable
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ژورنال
عنوان ژورنال: Fundamental Toxicological Sciences
سال: 2023
ISSN: ['2189-115X']
DOI: https://doi.org/10.2131/fts.10.21