Health Sciences Division, Universidad de Guanajuato Campus León, León, Guanajuato, Mexico.
Toxicol Lett. 2012 Apr 25;210(2):254-63. doi: 10.1016/j.toxlet.2012.01.021. Epub 2012 Feb 8.
CYP2E1, an inducible enzyme present in different human tissues, metabolizes several potentially toxic substances including many volatile organic compounds (VOCs). One indirect way to monitor exposure to VOCs may be, therefore, the assessment of CYP2E1 activity in vivo using the chlorzoxazone (CHZ) test.
To compare CYP2E1 activity in two groups of workers: one with a known occupational exposure to VOCs (exposed group) and the other employed in administrative tasks at two universities (control group) from the city of León, Guanajuato, México.
(1) Passive diffusion monitors were used to evaluate individual levels of exposure to toluene, benzene and ethylbenzene in 48 persons (24 tannery workers and 24 administrative controls) during a 8h work shift; (2) after 12h fasting 500mg CHZ, a selective probe for assessing CYP2E1 activity, was orally administered and, after 2h, a venous blood sample was collected for HPLC plasmatic quantitative determination of CHZ and its mean metabolite 6-hydroxychlorzoxazone.
Toluene mean exposure levels were higher in the exposed group (2.86±2ppm vs. 0.05±0.005ppm; p<0.001). Also, in this group CYP2E1 activity was lower (p<0.05) and it decreased as the accumulated months of labor exposure increased (negative correlation, p<0.05). These results are in line with previous findings obtained from shoemakers exposed to various solvents but, interestingly, they are partly in contrast with those of another study in printers.
In spite of the relatively low levels of toluene exposure found for tannery workers, an effect on CYP2E1 activity was evident. Although the mechanism of this interaction is still unknown, the decrease in CYP2E1 activity per se might represent a health risk, considering that these workers may be less protected against other CYP2E1 substrates present in the labor setting or derived from an intentional exposure.
比较两组工人的 CYP2E1 活性:一组已知职业接触挥发性有机化合物(VOCs)(暴露组),另一组在墨西哥瓜纳华托州莱昂市的两所大学从事行政工作(对照组)。
(1)在 8 小时工作班次期间,使用被动扩散监测器评估 48 人(24 名制革工人和 24 名行政对照者)个体接触甲苯、苯和乙苯的水平;(2)禁食 12 小时后,口服 500mg 氯唑沙宗(一种评估 CYP2E1 活性的选择性探针),2 小时后采集静脉血样,用 HPLC 法测定氯唑沙宗及其代谢物 6-羟基氯唑沙宗的血浆定量。
暴露组甲苯的平均暴露水平较高(2.86±2ppm 对 0.05±0.005ppm;p<0.001)。此外,该组 CYP2E1 活性较低(p<0.05),随着接触劳动月份的增加而降低(负相关,p<0.05)。这些结果与以前从接触各种溶剂的鞋匠中获得的结果一致,但有趣的是,它们与另一项关于印刷工的研究结果部分相反。
尽管制革工人接触甲苯的水平相对较低,但 CYP2E1 活性受到明显影响。尽管这种相互作用的机制尚不清楚,但 CYP2E1 活性的降低本身可能代表一种健康风险,因为这些工人可能对劳动环境中存在的其他 CYP2E1 底物或来自故意暴露的 CYP2E1 底物的保护作用降低。