Guzelian P S
Environ Health Perspect. 1985 May;60:159-64. doi: 10.1289/ehp.8560159.
An unresolved question is whether humans exposed to comparatively low doses of persistent environmental chemicals such as polyhalogenated biphenyls or organochlorine pesticides are at risk for injury to the liver. Cross-sectional epidemiologic studies suggest that these chemicals may produce statistically significant but clinically mild abnormalities in the commonly employed chemical tests of liver function. The few reports of human liver morphology reveal nonspecific changes reflecting effects of lipophilic chemicals. There is evidence that chemicals of this category in at least some doses cause induction of liver microsomal enzymes involved in biotransformation of foreign substances. This finding has been documented by measurements of the clearance of model drugs or the appearance in the urine of steroid metabolites or glucaric acid. Although a positive statistical correlation between the concentrations of these chemicals in serum and the serum gamma-glutamyltranspeptidase activity has been reported, the non-specificity of the latter enzyme precludes conclusion that this change is indicative of induction of liver microsomal enzymes. Although the effects of this type of environmental chemical are not indicative of progressive liver disease, only prospective clinical trials can resolve the issue of the risk for future development of liver malignancy.
一个尚未解决的问题是，接触相对低剂量的持久性环境化学物质（如多卤联苯或有机氯农药）的人是否有肝脏受损的风险。横断面流行病学研究表明，这些化学物质可能在常用的肝功能化学检测中产生具有统计学意义但临床上轻微的异常。关于人类肝脏形态的少数报告显示出反映亲脂性化学物质作用的非特异性变化。有证据表明，至少某些剂量的此类化学物质会导致参与外源物质生物转化的肝脏微粒体酶的诱导。这一发现已通过对模型药物清除率的测量或类固醇代谢物或葡萄糖醛酸在尿液中的出现得到证实。尽管已报道血清中这些化学物质的浓度与血清γ-谷氨酰转肽酶活性之间存在正相关统计关系，但后一种酶的非特异性排除了得出这种变化表明肝脏微粒体酶诱导的结论。虽然这类环境化学物质的影响并不表明存在进行性肝病，但只有前瞻性临床试验才能解决未来发生肝脏恶性肿瘤风险的问题。
