FACTORS AFFECTING HPRT MUTANT FREQUENCY IN T-LYMPHOCYTES OF SMOKERS AND NONSMOKERS

The frequency of thioguanine-resistant, hypoxanthine phosphoribosyltra nsferase-deficient lymphocytes in the peripheral blood of human subjec ts was used to study the genotoxic effects of smoking. Sixty-two nonsm okers and 58 smokers, aged 19 to 45 years with average ages of 30 and 32 years, respectively, and with no other known exposures, were studie d using an in vitro assay of the frequency of mutant lymphocyte clones . Analysis of variance explained 68% of the variation in the mutant fr equencies. Mutant frequency was dependent upon lymphocyte cloning effi ciency, length of smoking history, age, and interactions between these variables. Four nonsmokers and three smokers had high mutant frequenc ies that were not explained by these variables. Mutant frequencies wer e inversely related to lymphocyte cloning efficiencies; the effect was twice as great for smokers as for nonsmokers. The time-dependent effe ct of smoking dominated, with mutant frequency increasing 10%/year of smoking as compared with an independent 1%/year of age. Smoking had a greater effect on young smokers' lymphocytes. Heterogeneity of mutant frequency among both smokers and nonsmokers and its implications for u se of lymphocyte mutation assays as biomarkers are discussed.