Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Toxicol Appl Pharmacol. 2012 Dec 15;265(3):308-15. doi: 10.1016/j.taap.2012.08.031. Epub 2012 Sep 10.
Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n=120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P≤0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P≤0.05) and PON1 192 (P≤0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal.
动物研究表明，对氧磷酶 1（PON1）基因型可能影响有机磷农药毒死蜱（CPF）的易感性。然而，蒙特卡罗分析表明，在人类低暴露条件下，PON1 基因型可能不会影响 CPF 相关毒性。本研究旨在确定 PON1 基因型对血液胆碱酯酶活性的影响，以及 CPF 暴露对接触 CPF 的工人血清 PON1 的影响。从埃及 Menoufia 省的农业工人（n=120）中采集唾液、血液和尿液，以确定 PON1 基因型、血液胆碱酯酶活性、对氯氧磷（CPOase）和对氧磷（POase）的血清 PON1 活性，以及 CPF 代谢物 3,5,6-三氯-2-吡啶醇（TCPy）的尿水平。PON1 55（P≤0.05）但不是 PON1 192 基因型对 CPOase 活性有显著影响。然而，PON1 55（P≤0.05）和 PON1 192（P≤0.001）基因型对 POase 活性均有显著影响。CPF 应用后 AChE 和 BuChE 明显受到抑制；然而，当调整 CPF 暴露（根据尿 TCPy 水平确定）和按 PON1 基因型分层时，CPOase 活性和 POase 活性均与 ChE 抑制无关。尽管在特定基因型组中存在活性变化，但 CPOase 和 POase 活性也不受 CPF 暴露的影响。总之，这些结果表明，无论 PON1 基因型和活性如何，工人在接触本研究人群所经历的暴露条件下仍具有解毒氯氧磷的能力，而 CPF 暴露对 PON1 活性的影响很小。
