Distribution and reproducibility of aryl hydrocarbon hydroxylase inducibility in a prospective population study of middle-aged male smokers and nonsmokers.

Abstract

Aryl hydrocarbon hydroxylase (AHH) inducibility was determined in a lymphoblast test system in 2,000 consecutive middle-aged male smokers, 304 ex-smokers, and 218 never-smokers in the same birth-year cohorts. Intraindividual, intraobserver, and interobserver, as well as temporal, reproducibility was checked in a special double-blind quadruplet sample series from 20 other consecutive middle-aged men. The results showed a three-modal phenotype distribution of AHH inducibility with high (fold induction greater than or equal to 3.6), intermediate (2.6-3.6) and low (less than or equal to 2.5) levels ranging between 7.6% to 10.5%, 38.5% to 43.0%, and 46.5% to 53.9%, respectively, in all the smoking categories. The reproducibility of the measurements was excellent, with one-way variance in the order of 0.007 to 0.033, and the applied assay method can therefore be used in large-scale prospective population investigations. Such are required in order to establish a cause-effect association between high AHH inducibility and smoking-related malignancies of the respiratory tract and oral cavity, as has been suggested from earlier retrospective studies in more limited clinical materials of cancers and precanceroses of these varieties.