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Interindividual and Intraindividual Variations in Aryl Hydrocarbon Hydroxylase in Monocytes from Monozygotic and Dizygotic Twins

Chemistry [E. P., H. V. G.], Biometry [R. T.], and Biology [T. O., R. C. B.] Branches, National Cancer Institute, NIH, Bethesda, Maryland 20014, and Department of Pharmacology [E. S. V.], The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033

Interindividual and intraindividual variations in the basal and benz(a)anthracene-induced levels of aryl hydrocarbon hydroxylase (AHH) were investigated in cultured monocytes obtained from 10 sets of monozygotic and 17 sets of dizygotic normal adult twin volunteers. The values for basal levels and therefore for induction ratios were more variable than those of the induced level. The mean values for the induced levels ranged from 4.26 to 17.69. Intratwin differences in the induced levels were quite small within monozygotic and most dizygotic twins. However, several sets of dizygotic twins had much greater intratwin differences than did the monozygotic twins: these discordant dizygotic twins were responsible for raising heritability indices, which were between 0.57 (uncorrected) and 0.71 (corrected). Genetic factors accounted for approximately one-half to two-thirds of the total interindividual variation in AHH inducibility that occurred in this study, the other one-half to one-third of the total variation being attributable to environmental factors. Small intratwin differences among most dizygotic twins suggest that a relatively small number of genes may be involved in regulation of the induced AHH levels.

When the same twins were assayed on two to four different occasions at monthly intervals, basal level, induced level, and induction ratio varied from one occasion to the next, one value generally differing by 50%, and occasionally by as much as 100%, from one of the other values. Nevertheless, on repeated analysis of the same twin set, the magnitude of the difference within the twin set remained quite small, although the absolute values changed appreciably from one assay to the next. This large variation on repetition in the absolute induced value of AHH in the presence of a relatively small variation in the magnitude of the difference within a given twin set suggests that the absolute induced values are influenced significantly by as yet unidentified factors in the laboratory procedure that fluctuate at the different times of monocyte isolation and assay. These data also suggest that nonlaboratory environmental factors are generally negligible determinants of induced AHH level. On repetition, very little variation in the value of the difference between a given set of twins suggests that genetic factors play a very large role in determining the induced AHH value.

¹ To whom requests for reprints should be addressed, at Chemistry Branch, Building 37, Room 3E24, National Cancer Institute, NIH, Bethesda, Md. 20014.

Received 3/ 3/77. Accepted 7/22/77.

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