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

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The γH2AX DNA damage assay from a drop of blood

DNA double-strand breaks (DSB) and blocked replication forks activate the DNA damage response (DDR), a signaling pathway marked by phosphorylation of histone 2AX (H2AX). The phosphorylated form, γH2AX, accumulates at the site of damage and can be detected as foci by immunocytochemistry. Therefore, γH2AX is a sensitive and robust biomarker of DNA damage, notably DSB. Cells from peripheral blood ...

متن کامل

DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint.

Mitotic catastrophe is the response of mammalian cells to mitotic DNA damage. It produces tetraploid cells with a range of different nuclear morphologies from binucleated to multimicronucleated. In response to DNA damage, checkpoints are activated to delay cell cycle progression and to coordinate repair. Cells in different cell cycle phases use different mechanisms to arrest their cell cycle pr...

متن کامل

DNA Chemical Damage and Its Detected

The DNA chemical damage is a very important researching project in chemistry, life science and related fields. In this paper, the biological function of DNA damage, the reason causing damage and the detecting technology of DNA damage are summarized and discussed.

متن کامل

Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy

Previous studies have found that methylmercury can damage hippocampal neurons and accordingly cause cognitive dysfunction. However, a non-invasive, safe and accurate detection method for detecting hippocampal injury has yet to be developed. This study aimed to detect methylmercury-induced damage on hippocampal tissue using proton magnetic resonance spectroscopy. Rats were given a subcutaneous i...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: Fundamental Toxicological Sciences

سال: 2023

ISSN: ['2189-115X']

DOI: https://doi.org/10.2131/fts.10.21