Beatriz Geovana Leite Vacario, Isabely Mayara da Silva, Murilo Galvani Machado, Julia Fernandes Gois Orrutéa, Aline Graciele Henriques Campos, Rafaela Oliveira Matos, Ana Carolina Lopes Federige, Bruna Yukie Koizumi, Maikely Bruna Leite, Isabela Mitsu Suo Komori, Hellen dos Santos Jaques, Daniel Rech, Roberta Losi Guembarovski, Marla Karine Amarante, Juliana Mara Serpeloni, Carolina Panis
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Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity—TRAP, and nitric oxide metabolites—NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. 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引用次数: 0
摘要
接触农药是包括乳腺癌(BC)在内的多种疾病的危险因素。UGT2B7 酶参与农药的解毒,该基因中的 rs7438135(G > A)变异增加了其葡萄糖醛酸化的潜力,有助于中和氧化应激代谢物。在此,我们根据 228 名 BC 妇女的 UGT2B7 rs7438135 (G > A) 状态,研究了职业杀虫剂暴露对全身氧化应激生成的影响。q-PCR 调查了 rs7438135 变异的存在,并测量了血浆中的氧化应激标记物(脂质过氧化水平、总抗氧化能力-TRAP 和一氧化氮代谢物-NOx)。在变异体存在的几种临床病理条件下,包括高增殖指数(ki67)和高侵袭性肿瘤,农药暴露会导致全身脂质过氧化显著增加。在高ki67、孕酮受体阳性、高级别和三阴性/Luminal B肿瘤以及低风险分层患者中,NOx增加。TRAP在绝经期的年轻患者、三阴性/腔道B型肿瘤患者以及死亡和复发风险较低的分层患者中消耗殆尽。这些研究结果表明,该变异体的存在并不能保护BC患者免受杀虫剂诱导的氧化应激的影响。
Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene
Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity—TRAP, and nitric oxide metabolites—NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.
期刊介绍:
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.