Objective: To determine if mtDNA damage can serve as a biomarker of prior pesticide exposure.

Background: Mitochondrial dysfunction is a hallmark of PD, and exposure to the insecticide and mitochondrial poison rotenone has been associated with PD risk [1]. Because long-term biomarkers do not exist for most xenobiotics, exposure determination has relied on self-report, which is subject to bias and may not reflect relevant biological exposures. We hypothesized that mtDNA damage may serve as a biomarker of past exposure to rotenone.

Method: We recruited people with PD (PwPD) and matched controls from the Agricultural Health Study, a cohort of pesticide applicators and their spouses. PD was determined by expert exam, and rotenone usage by interview. DNA derived from blood buffy-coat samples was analyzed in a blinded manner using a quantitative polymerase chain reaction (QPCR)-based assay that simultaneously measures multiple forms of mtDNA damage [2]. We tested associations of log-transformed mtDNA lesion frequency and prior rotenone use using multiple linear regression, adjusting for PD status, age, gender, and smoking.

Results: Complete data were available for 85 individuals (44 PwPD, 41 controls; 75 men), 34 of whom had mixed or applied rotenone (17 PwPD, 17 controls). In univariate analyses, mtDNA lesion frequency was slightly greater in PwPD than in controls (mean 0.70, SD 0.53 vs. 0.60, SD 0.45). In adjusted analyses, rotenone use was associated with greater mtDNA damage overall (β=0.37, p=0.06). The association was stronger in men (β=0.49, p=0.02). Associations with rotenone tended to be stronger in PwPD than in controls (all cases β=0.59, p=0.12; male cases β=0.72, p=0.068; all controls β=0.22, p=0.36; male controls β=0.34, p=0.2).

Conclusion: Although based on a relatively small sample, mtDNA lesion frequency was greater in both cases and controls exposed to rotenone, particularly in men. Mitochondrial lesion frequency also appeared to be greater in PwPD. MtDNA damage may serve as an unbiased, long-term biomarker for exposure to rotenone, and possibly to other mitochondrial toxicants.

References: 1. Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW. Rotenone, Paraquat, and Parkinson’s Disease. Environmental Health Perspectives. 2011;119(6):866-72. 2. Sanders LH, Howlett EH, McCoy J, Greenamyre JT. Mitochondrial DNA damage as a peripheral biomarker for mitochondrial toxin exposure in rats. Toxicol Sci. 2014;142(2):395-402.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rotenone-exposure-is-associated-with-mitochondrial-dna-mtdna-damage-in-humans/