GENETIC-CONTROL OF INTERINDIVIDUAL VARIATIONS IN INDUCIBILITY OF ARYL-HYDROCARBON HYDROXYLASE IN CULTURED HUMAN LYMPHOCYTES

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (12) , 4619-4630
Abstract
Interindividual and intraindividual variations in aryl hydrocarbon hydroxylase (AHH) induction by the carcinogen 3-methylcholanthrene were studied in cultured lymphocytes from normal adult volunteers. Using 8 pairs of monozygotic and 8 pairs of dizygotic twins, the extent to which these variations are controlled by heritable factors and whether AHH inducibility correlates in an individual with the plasma half-lives of 3 drugs was examined. 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 a single lot of fetal calf serum (0.77) suggests that genetic rather than environmental factors are 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 < P < 0.05) occurs between AHH inducibility in culture and the plasma antipyrine half-life, but not between AHH inducibility and phenylbutazone or bishydroxycoumarin half-lives.