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Time of the day dictates the variability of biomarkers of exposure to disinfection byproducts
Environment International ( IF 10.3 ) Pub Date : 2017-12-13 , DOI: 10.1016/j.envint.2017.12.013
Stephanie Gängler , Pantelis Charisiadis , Ratanesh Seth , Saurabh Chatterjee , Konstantinos C. Makris

Non-persistent environmental chemicals (NOPEC) are xenobiotics with short half-lives of elimination (< 7 h). Similar to chronopharmacokinetics, NOPEC metabolism may follow diurnal patterns of cytochrome P450 activity. The role of circadian liver clock in shaping NOPEC metabolism and their concomitant measurements of biomarkers of exposure and effect remains poorly understood in real-life human settings. Metabolic activation (toxication) by CYP2E1 converts trihalomethanes (THM) to harmful metabolites. We investigated the diurnal variation of urinary THM exposures and their metabolism patterns as catalyzed by CYP2E1 redox activity, using the surrogate marker of 4-hydroxynonenal (4HNE). We implemented three time-series trials with adult volunteers conducting specific household cleaning activities at predefined times of a day. Circadia variation of 4HNE was assessed with a cosinor model and its mesor levels increased with THM exposure. The time of exposure within the day dictated the magnitude of urinary THM levels and their toxication effect; in all three trials and relative to urinary THM levels before the activity, lower and higher median THM were measured right after the activity in morning and afternoon/night, respectively. This is consistent with higher reported CYP2E1 redox activity in light/active phase. Population health studies should incorporate time-stamped biomarker data to improve the understanding of chronic disease processes.



中文翻译:

一天中的时间决定着暴露于消毒副产物的生物标志物的变异性

非持久性环境化学品(NOPEC)是具有短半衰期消除(<7小时)的异生物素。与时间药代动力学相似,NOPEC代谢可能遵循细胞色素P450活性的昼夜模式。在现实的人类环境中,人们对昼夜节律性肝钟在塑造NOPEC代谢中的作用及其伴随的暴露和效应生物标志物的测量仍知之甚少。CYP2E1的代谢活化(中毒)将三卤甲烷(THM)转化为有害的代谢物。我们使用4-羟基壬烯醛(4HNE)替代标记物调查了CYP2E1氧化还原活性催化的尿液THM暴露及其代谢模式的日变化。我们对成年志愿者进行了三个时间序列试验,这些成年志愿者在一天的预定时间进行特定的家庭清洁活动。用余弦模型评估了4HNE的昼夜节律变化,其中值水平随THM暴露而增加。一天中的暴露时间决定了尿液THM的水平及其毒性作用。在所有这三个试验中,以及相对于活动前尿液中THM的水平,分别在活动后早上和下午/晚上测量了较低和较高的THM中值。这与在光/活性相中报道的较高的CYP2E1氧化还原活性一致。人群健康研究应纳入带有时间戳的生物标记数据,以增进对慢性疾病过程的了解。在所有这三个试验中,以及相对于活动前尿液中THM的水平,分别在活动后早上和下午/晚上测量了较低和较高的THM中值。这与在光/活性相中报道的较高的CYP2E1氧化还原活性一致。人群健康研究应纳入带有时间戳的生物标记数据,以增进对慢性疾病过程的了解。在所有这三个试验中,以及相对于活动前尿液中THM的水平,分别在活动后早上和下午/晚上测量了较低和较高的THM中值。这与在光/活性相中报道的较高的CYP2E1氧化还原活性一致。人群健康研究应纳入带有时间戳的生物标记数据,以增进对慢性疾病过程的了解。

更新日期:2017-12-14
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