Genetic control of interindividual variations in the inducibility of aryl hydrocarbon hydroxylase in cultured human lymphocytes.
Genetic control of interindividual variations in the inducibility of aryl hydrocarbon hydroxylase in cultured human lymphocytes.
复制标题
培养的人淋巴细胞中芳烃羟化酶诱导能力的个体差异的遗传控制。
作者：
S. Atlas;E. Vesell;D. Nebert
研究了3-甲基胆蒽诱导正常成人淋巴细胞芳烃羟化酶（AHH）的个体间和个体内差异。使用8对单卵双胞胎和8对双卵双胞胎，我们研究了这些变化在多大程度上受遗传因素的控制，以及AHH是否诱导个体与三种药物的血浆半衰期的相关性。如果不考虑测定标准曲线的非线性，可能会发生诱导比（诱导倍数）的显著高估。倍数诱导仍然相对恒定的个人，但大的个体内的变化发生在绝对的“控制”和“诱导”AHH活动。胎牛血清可能含有AHH活性的诱导剂，其随特定批次的血清而变化，从而使表观诱导率成为对3-甲基胆蒽诱导的遗传易感性的不精确指标。用不同批次胎牛血清（0.80）或单一批次胎牛血清（0.77）研究的双胞胎中AHH诱导倍数的遗传力指数表明，尽管如此，遗传因素而不是环境因素主要负责人淋巴细胞中3-甲基胆蒽诱导AHH的个体间变异。在这些双胞胎中，AHH诱导的培养物和血浆安替比林半衰期之间存在显著但较差的相关性（r=-0.551; 0.03小于p <0.05），但AHH诱导的培养物和保泰松或双羟基香豆素半衰期之间不存在相关性。
Interindividual and intraindividual variations in aryl hydrocarbon hydroxylase (AHH) induction by 3-methylcholanthrene were studied in cultured lymphocytes from normal adult volunteers. Using eight pairs of monozygotic and eight pairs of dizygotic twins, we examined to what extent these variations are controlled by heritable factors and whether AHH inducibility correlations in an individual with the plasma half-lives of three drugs. Substantial overestimation of the induction ratio (fold inducibility) may occur if the nonlinearity of the assay standard curve is not considered. Fold inducibility remains relatively constant for an individual, but large intraindividual variations occur in absolute "control" and "induced" AHH activities. Fetal calf serum may contain inducers of AHH activity that vary with the particular lot of serum, thereby rendering the apparent induction ratio an imprecise indicator of genetic susceptibility to induction by 3-methylcholanthrene. The index of heritability for AHH fold inducibility in twins studied with different lots of fetal calf serum (0.80) or with a single lot of fetal calf serum (0.77) suggests nonetheless that genetic rather than environmental factors are mainly responsible for interindividual variations in AHH inducibility by 3-methylcholanthrene in human lymphocytes. In these twins a significant but poor correlation (r=-0.551; 0.03 less than p less than 0.05) occurs between AHH inducibility in culture and the plasma antipyring half-life, but not between AHH inducibility and phenylbutazone or bishdroxycoumarin half-lives.