Silvestre Rafaele Tavares, Bravo Maryah, Santiago Fabio, Delmonico Lucas, Scherrer Luciano, Otero Ubirani Barros, Liehr Thomas, Alves Gilda, Chantre-Justino Mariana, Ornellas Maria Helena
Pak J Biol Sci. 2020 Mar;23(4):518-525. doi: 10.3923/pjbs.2020.518.525.
Gas station attendants are occupationally exposed to benzene, toluene, ethylbenzene and xylene (BTEX) compounds and thus more susceptible to the biological effects of this mixture present in gasoline, especially due to the carcinogenicity of benzene. Furthermore, the harmful effects of BTEX exposure may be potentiated by genetic and epigenetic inactivation of critical genes. The objective was to evaluate such gene-BTEX interactions accessing the promoter methylation status of p14ARF, p16INK4A and GSTP1 in peripheral blood leukocyte samples.
The 59 exposed and 68 unexposed participants from Rio de Janeiro, Brazil, were included. The promoter methylation status was accessed by methylation-specific PCR (MSP) and GSTP1 Ile105Val polymorphism was investigated by PCR-restriction fragment length polymorphism (PCR-RFLP) technique.
Both p14ARF and p16INK4A were significantly hypermethylated in exposed subjects compared to unexposed (p = 0.004 and p<0.001, respectively). Additionally, p16INK4A hypermethylation in the exposed group was correlated with chromosomal abnormalities (CAs) (p = 0.018), thus highlighting the influence of the gene-environment interactions on genome instability. Noteworthy, p16INK4A methylation was significantly associated with miscarriage among female attendants (p = 0.047), in which those who reported miscarriage exhibited hypermethylation in at least 2 of the 3 genes analyzed. The GSTP1 heterozygote genotype, which could affect the metabolism of benzene detoxification, was found in both groups but was more frequent in those occupationally exposed. No significant association was observed between GSTP1 genotypes and methylation status.
Together, these findings indicate that gas station attendants with the aforementioned epigenetic and genetic profiles may be at greater risk of occupational BTEX exposure-induced genome instability, which could require concerted efforts to establish more preventive actions and constant biomonitoring in gas station attendants.
加油站工作人员职业性接触苯、甲苯、乙苯和二甲苯（BTEX）化合物，因此更容易受到汽油中这种混合物的生物学影响，尤其是由于苯具有致癌性。此外，关键基因的遗传和表观遗传失活可能会增强BTEX暴露的有害影响。目的是通过检测外周血白细胞样本中p14ARF、p16INK4A和GSTP1的启动子甲基化状态来评估此类基因与BTEX的相互作用。
纳入了来自巴西里约热内卢的59名暴露者和68名未暴露者。通过甲基化特异性PCR（MSP）检测启动子甲基化状态，并通过PCR-限制性片段长度多态性（PCR-RFLP）技术研究GSTP1 Ile105Val多态性。
与未暴露者相比，暴露者中p14ARF和p16INK4A均显著高甲基化（分别为p = 0.004和p<0.001）。此外，暴露组中p16INK4A高甲基化与染色体异常（CAs）相关（p = 0.018），从而突出了基因-环境相互作用对基因组不稳定性的影响。值得注意的是，p16INK4A甲基化与女性工作人员流产显著相关（p = 0.047），其中报告流产的女性在分析的3个基因中至少有2个表现出高甲基化。两组均发现了可能影响苯解毒代谢的GSTP1杂合子基因型，但在职业暴露者中更常见。未观察到GSTP1基因型与甲基化状态之间存在显著关联。
总之，这些发现表明，具有上述表观遗传和遗传特征的加油站工作人员可能面临更高的职业性BTEX暴露诱导的基因组不稳定性风险，这可能需要共同努力，为加油站工作人员制定更多预防措施并持续进行生物监测。
