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The role of B7 costimulation in benzene immunotoxicity and its potential association with cancer risk
Environmental Research ( IF 7.7 ) Pub Date : 2018-06-06 , DOI: 10.1016/j.envres.2018.05.029
Elisa Sauer , Bruna Gauer , Sabrina Nascimento , Jessica Nardi , Gabriela Göethel , Bárbara Costa , Douglas Correia , Ursula Matte , Mariele Charão , Marcelo Arbo , Albert Duschl , Angela Moro , Solange Cristina Garcia

Benzene is a recognized human carcinogen; however, there are still some gaps in the knowledge regarding the mechanism of toxicity of this organic solvent and potential early biomarkers for the damage caused by it. In a previous study, our research group demonstrated that the adhesion molecules of the immune system (B7.1 and B7.2) could be potential biomarkers in the early detection of immunotoxicity caused by benzene exposure. Therefore, this study was developed to deepen the understanding regarding this important topic, aiming to contribute to the comprehension of the benzene toxicity mechanism mediated by B7.1 and B7.2 and its potential association with the risk of carcinogenicity. B7.1 and B7.2 protein expression in blood monocytes and B7.1 and B7.2 gene expression in PBMCs were evaluated. Additionally, complement C3 and C4 levels in serum were measured, as well as p53 gene expression in PBMCs. Seventy-four gas station workers (GSW group) and 71 non-occupationally exposed subjects (NEG) were evaluated. Our results demonstrated decreased levels of B7.1 and B7.2 protein and gene expression in the GSW group compared to the NEG (n = 71) (p < 0.01). Along the same lines, decreased levels of the complement system were observed in the GSW group (p < 0.01), demonstrating the impairment of this immune system pathway as well. Additionally, a reduction was observed in p53 gene expression in the GSA group (p < 0.01). These alterations were associated with both the benzene exposure biomarker evaluated, urinary trans, trans-muconic acid, and with exposure time (p < 0.05). Moreover, strong correlations were observed between the gene expression of p53 vs. B7.1 (r = 0.830; p < 0.001), p53 vs. B7.2 (r = 0.685; p < 0.001), and B7.1 vs. B7.2 (r = 0.702; p < 0.001). Taken together, these results demonstrate that the immune system co-stimulatory molecule pathway is affected by benzene exposure. Also, the decrease in p53 gene expression, even at low exposure levels, reinforces the carcinogenicity effect of benzene in this pathway. Therefore, our results suggest that the promotion of immune evasion together with a decrease in p53 gene expression may play an important role in the benzene toxicity mechanism. However, further and targeted studies are needed to confirm this proposition.



中文翻译:

B7共刺激在苯免疫毒性中的作用及其与癌症风险的潜在关联

苯是公认的人类致癌物;然而,关于这种有机溶剂的毒性机理以及潜在的早期生物标记物对其造成的损害的认识仍然存在空白。在先前的研究中,我们的研究小组证明了免疫系统的粘附分子(B7.1和B7.2)可能是早期检测由苯暴露引起的免疫毒性的潜在生物标志物。因此,本研究的开展是为了加深对这一重要主题的理解,旨在促进对B7.1和B7.2介导的苯毒性机制及其与致癌性风险的潜在关联的理解。评估了血液单核细胞中B7.1和B7.2蛋白的表达以及PBMC中B7.1和B7.2基因的表达。此外,测量了血清中补体C3和C4的水平,以及PBMC中p53基因的表达。评估了74名加油站工作人员(GSW组)和71名非职业接触的受试者(NEG)。我们的研究结果表明,与NEG相比,GSW组的B7.1和B7.2蛋白质和基因表达水平下降(n = 71)(p  <0.01)。同样,在GSW组中观察到补体系统水平降低(p  <0.01),也表明该免疫系统途径也受到损害。另外,在GSA组中观察到p53基因表达降低(p  <0.01)。这些改变与所评估的苯暴露生物标志物,尿液反式,反粘康酸以及暴露时间有关(p  <0.05)。此外,在p53与B7.1(r = 0.830; p  <0.001),p53与B7.2(r = 0.685; p  <0.001)和B7.1与B7的基因表达之间观察到强相关性。.2(r = 0.702; p <0.001)。综上所述,这些结果表明免疫系统共刺激分子途径受苯暴露的影响。同样,即使在低暴露水平下,p53基因表达的降低也增强了该途径中苯的致癌作用。因此,我们的结果表明,促进免疫逃逸以及降低p53基因表达可能在苯毒性机制中起重要作用。但是,需要进一步的针对性研究来证实这一主张。

更新日期:2018-06-06
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