Abstract：
As the mitochondrial DNA copy number (mtDNAcn) has been reported to be a biomarker for mtDNA damage in honeybees when exposed to sublethal neonicotinoids, the feasibility of using human mitochondria as a predictor upon neonicotinoid exposure remains elusive. This study investigated the association between the urinary neonicotinoid and the relative mtDNAcn (RmtDNAcn) of oral epithelial cells collected in a cross-sectional study with repeated measurements over 6 weeks. The molecular mechanism underlying neonicotinoid-caused mitochondrial damage was also examined by in vitro assay. Herein, the average integrated urinary neonicotinoid (IMIRPF) concentration ranged from 8.01 to 13.70 μg/L (specific gravity-adjusted) during the sampling period. Concomitantly, with an increase in the urinary IMIRPF, the RmtDNAcn significantly increased from 1.20 (low group) to 1.93 (high group), indicating potential dose-dependent mitochondrial damage. Furthermore, the linear regression analysis confirmed the significant correlation between the IMIRPF and RmtDNAcn. Results from in vitro assays demonstrated that neonicotinoid exposure led to the inhibition of the genes encoding mitochondrial oxidative phosphorylation (OXPHOS) complexes I and III (e.g., ND2, ND6, CytB, and CYC1), accompanied by increased reactive oxygen species production in SH-SY5Y cells. Conjointly, neonicotinoid exposure led to mitochondrial dysfunction and a resulting increase in the RmtDNAcn, which may serve as a plausible biomarker in humans.
摘要：
由于线粒体DNA拷贝数（mtDNAcn）已被报道为暴露于亚致死的新烟碱类物质时蜜蜂中mtDNA损伤的生物标志物，使用人线粒体作为新烟碱暴露预测因子的可行性仍然难以捉摸。这项研究调查了在横断面研究中收集的尿液新烟碱与口腔上皮细胞的相对mtDNAcn（RmtDNAcn）之间的关联，并在6周内进行了重复测量。还通过体外测定检查了新烟碱引起的线粒体损伤的分子机制。在这里，在采样期间,平均尿中新烟碱类(IMIRPF)浓度范围为8.01~13.70μg/L(比重调整).同时，随着尿IMIRPF的增加，RmtDNAcn从1.20（低组）显着增加到1.93（高组），表明潜在的剂量依赖性线粒体损伤。此外，线性回归分析证实了IMIRPF和RmtDNAcn之间的显著相关性。体外测定的结果表明，新烟碱类暴露导致编码线粒体氧化磷酸化（OXPHOS）复合物I和III的基因受到抑制（例如，ND2,ND6,CytB,和CYC1），伴随着SH-SY5Y细胞中活性氧产生的增加。同时，新烟碱暴露导致线粒体功能障碍，并导致RmtDNAcn增加，它可以作为人类的一个合理的生物标志物。
