Polycyclic aromatic hydrocarbon (PAH) exposure and genetic susceptibility were conductive to genotoxic effects including gene damage, which can increase mutational probability. We aimed to explore the dose-effect associations of PAH exposure with damage of exons of epidermal growth factor receptor (EGFR) and breast cancer susceptibility gene 1 (BRCA1), as well as their associations whether modified by Flap endonuclease 1 (FEN1) genotype. Two hundred eighty-eight coke oven male workers were recruited, and we detected the concentration of 1-hydroxypyrene (1-OH-pyr) as PAH exposure biomarker in urine and examined base modification in exons of EGFR and BRCA1 respectively, and genotyped FEN1 rs174538 polymorphism in plasma. We found that the damage indexes of exon 19 and 21 of EGFR (EGFR-19 and EGFR-21) were both significantly associated with increased urinary 1-OH-pyr (both Ptrend < 0.001). The levels of urinary 1-OH-pyr were both significantly associated with increased EGFR-19 and EGFR-21 in both smokers and nonsmokers (both P < 0.001). Additionally, we observed that the urinary 1-OH-pyr concentrations were linearly associated with both EGFR-19 and EGFR-21 only in rs174538 GA+AA genotype carriers (both P < 0.001). Moreover, FEN1rs rs174538 showed modifying effects on the associations of urinary 1-OH-pyr with EGFR-19 and EGFR-21 (both Pinteraction < 0.05). Our findings revealed the linear dose-effect association between exon damage of EGFR and PAH exposure and highlight differences in genetic contributions to exon damage and have the potential to identify at-risk subpopulations who are susceptible to adverse health effects induced by PAH exposure.
Environmental Science and Pollution Research - With high groundwater levels, coal–grain overlap areas (CGOAs) are vulnerable to subsidence and water logging during mining activities, thereby... 相似文献
Four chlorobenzenes (chlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene, p-chloro-methylbenzene) were administrated to the crucian carps (Carassius auratus) by peritoneal injections in the laboratory for 30 days. Serum testosterone and 17 beta-estradiol concentrations were detected using radioimmunology assay (RIA), and the activities of two hepatic microsome enzymes, glutathione s-transferase (GST) and UDP-glucuronosyltransferase (UDPGT), were measured using the modified methods as described by Habig and Owens. Results showed that the four chlorobenzenes caused significant increases in serum testosterone concentration in the crucian carps (P < 0.05) compared to the controls, but they caused no significant effect on 17 beta-estradiol level. All test chemicals caused a change in hepatic GST activity in crucian carps, with significant increases in enzyme activity (P < 0.05). Chlorobenzene, 1,3-dichlorobenzene and p-chloro-methylbenzene resulted in a marked inhibition to UDPGT activity in crucian carp (P < 0.05) except 1,4-dichlorobenzene. The changes in hepatic microsome enzyme activities may have resulted in the alterations of serum sex steroids levels in the crucian carps. The results indicated that these four chlorobenzenes may result in the changes of endocrine functions and may affect the reproductive success of this and other species. 相似文献