Wang C H, Singh S M
Can J Genet Cytol. 1985 Apr;27(2):158-64. doi: 10.1139/g85-024.
Most genetic studies on individual and racial differences in sensitivity to alcohol intoxication have concentrated on genetic variations associated with structural genes for the enzymes involved in alcohol metabolism, including alcohol dehydrogenase (ADH; E.C. 1.1.1.1). We studied the ethanol-induced regulation of ADH following chronic administration of ethanol in mice. Newly weaned males from six inbred strains (BALB/c, C3H/HeSnJ, C3H/S, C57BL/6J, S.W., and 129/ReJ) were subjected to ethanol administration. Alterations in the level of liver ADH activity, relative to matched littermate controls, were evaluated. The change in ADH activity was found to be strain (genotype) specific, which may explain the contradictory results in the literature. Strains which showed induction of ADH activity, in general, reflected a strain-specific time-dependent profile. Strains which showed repression, however, were independent in the degree of repression to the duration of ethanol exposure. Such variable, ethanol-induced regulatory responses (induction/repression) in ADH activity of different genotypes may account for individual and population variations in response to alcohol. Additional work, however, is needed to establish the molecular bases of ADH inducibility and its specific role in relative susceptibility to alcohols.
大多数关于个体和种族对酒精中毒敏感性差异的遗传学研究都集中在与酒精代谢相关酶的结构基因的遗传变异上，这些酶包括乙醇脱氢酶（ADH；E.C. 1.1.1.1）。我们研究了小鼠长期给予乙醇后乙醇诱导的ADH调节作用。选用来自六个近交系（BALB/c、C3H/HeSnJ、C3H/S、C57BL/6J、S.W.和129/ReJ）的刚断奶雄性小鼠进行乙醇给药。相对于匹配的同窝对照，评估肝脏ADH活性水平的变化。发现ADH活性的变化具有品系（基因型）特异性，这可能解释了文献中相互矛盾的结果。一般来说，表现出ADH活性诱导的品系反映出品系特异性的时间依赖性特征。然而，表现出抑制作用的品系在抑制程度上与乙醇暴露持续时间无关。不同基因型的ADH活性中这种可变的、乙醇诱导的调节反应（诱导/抑制）可能解释了个体和群体对酒精反应的差异。然而，还需要进一步的研究来确定ADH诱导性的分子基础及其在对酒精相对易感性中的具体作用。
