PARP1-DNMT1-CTCF complex and the apoptotic-induced factor mRNA expressions in workers occupationally exposed to
Mona Salah El-Din Habieb1, Faten Ezzelarab Younis2, Manal Safan1
1Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin Al-Kom, Menoufia, Egypt.
Abstract:
Exposure to benzene is a common occupational hazard as well as a hematopoietic system intoxicant, but the entire picture of its molecular pathogenesis is still hazy. Its leukemogenic effect could be attributed to DNA damage, decreased repair capacity, altered methylation patterns, and defective apoptosis. Poly ADP-ribose polymerase1, DNA methyltransferase1, and CCCTC-binding factor (PARP1-DNMT1-CTCF) complex play an essential role in methylation maintenance and DNA damage repair response. This study aimed to assess the expression of PARP1, PAR glycohydrolases (PARG), DNMT1, CTCF, and apoptosis-inducing factor (AIF) in subjects occupationally exposed to benzene. A total of 200 subjects were enrolled in this study: 100 workers occupationally exposed to benzene (painters and decorators) and 100 unexposed office workers. Occupational exposure data were obtained. The biochemical and hematological evaluations were done. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to assess mRNA expression of PARP1, PARG, DNMT1, CTCF, and AIF. Both biochemical and hematological parameters were within normal limits; workplace benzene air concentration was significantly higher in exposed workers than the levels among controls (P < 0.001). Significant decrease in mRNA levels of PARP1, DNMT1, CTCF, and AIF was noticed among the exposed group (P = 0.01, P < 0.001, P = 0.004, P < 0.001, respectively) in comparison with the control group, while PARG showed non-significant difference (P = 0.16). There was a significant negative correlation between workplace benzene air concentration and expression levels of PARP1, DNMT1, and AIF. The reduced expression of PARP1, DNMT1, CTCF, and AIF observed in exposed workers may represent one of the first benzene-induced changes that might threaten erythropoiesis.
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