Korea Food and Drug Administration, Korea Food and Drug Administration, Seoul, South Korea.
J Toxicol Environ Health A. 2009;72(21-22):1352-68. doi: 10.1080/15287390903212550.
The primary objective of this study was to develop exposure biomarkers that "correlate with the endocrine-disrupting effects induced by methoxyclor (MTC), an organochlorine pesticide, using" urinary (1)H nuclear magnetic resonance (NMR) spectral data. Exposure biomarkers play an important role in risk assessment. MTC is an environmental endocrine disruptor with estrogenic, anti-estrogenic, and anti-androgenic properties. A new approach of proton nuclear magnetic resonance ((1)H NMR) urinalysis using pattern recognition was proposed for exposure biomarkers of MTC in female rats. The endocrine disruptor was expected to induce estrogenic effects in a dose dependent manner which, was confirmed by the uterotrophic assay. MTC [50, 100, or 200 m g/kg/d, orally (p.o.) or subcutaneously (s.c.)] was administered to ovariectomized female Sprague-Dawley (SD) rats for 3 d consecutively and urine was collected every 24 h. The animals were sacrificed 24 h after the last dose. All animals treated orally with MTC showed a significant increase in uterine and vaginal weight at all doses. However, in the s.c. route, only a high dose of 200 mg MTC/kg induced a significant increase in uterine and vaginal weight. (1)H NMR spectroscopy revealed evident separate clustering between pre- and post-treatment groups using global metabolic profiling through principal component analysis (PCA) and partial least square (PLS) discrimination analysis (DA) after different exposure routes. With targeted profiling, the endogenous metabolites of acetate, alanine, benzoate, lactate, and glycine were selected as putative exposure biomarkers for MTC. Data suggest that the proposed putative exposure biomarkers may be useful in a risk assessment of the endocrine-disrupting effects produced by MTC.
本研究的主要目的是开发暴露生物标志物，“使用”尿液（1）H 核磁共振（NMR）谱数据来“与甲氧基氯（MTC）引起的内分泌干扰效应相关联”，MTC 是一种有机氯农药，具有雌激素、抗雌激素和抗雄激素特性。本文提出了一种利用模式识别质子核磁共振（1）H NMR 尿液分析的新方法，用于检测雌性大鼠 MTC 的暴露生物标志物。该内分泌干扰物有望以剂量依赖的方式诱导雌激素效应，这一点通过子宫增重试验得到了证实。MTC[50、100 或 200mg/kg/d，口服（po）或皮下（sc）]连续 3 天给予去卵巢 Sprague-Dawley（SD）雌性大鼠，每 24 小时收集一次尿液。最后一次给药后 24 小时处死所有动物。所有经口给予 MTC 的动物在所有剂量下均表现出子宫和阴道重量显著增加。然而，在 sc 途径中，只有 200mg MTC/kg 的高剂量才会引起子宫和阴道重量的显著增加。通过主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）进行全局代谢谱分析，1H NMR 光谱揭示了不同暴露途径治疗前后组之间明显的分离聚类。通过靶向分析，选择了内源性代谢物乙酸盐、丙氨酸、苯甲酸、乳酸盐和甘氨酸作为 MTC 的潜在暴露生物标志物。数据表明，所提出的潜在暴露生物标志物可能有助于评估 MTC 产生的内分泌干扰效应的风险。
