Relationship between hprt mutant frequency, aromatic DNA adducts and genotypes for GSTM1 and NAT2 in bus maintenance...

We have studied the mutant frequency in the human gene for hypoxanthine-guanine phosphoribosyl transferase (hprt) using the T-cell cloning assay, the aromatic DNA adduct level using the 32P-postlabelling assay, and related the levels of these biomarkers to the genotypes for glutathione transferase (GST mu) and N-acetyltransferase (NAT2) in non-smoking bus maintenance workers exposed to diesel exhaust. No difference in mutant frequency was observed between the 47 exposed (8.6 x 10(-6), age range 27-65) and the 22 control individuals (8.4 x 10(-6), age range 23-61), while the difference in adduct level (3.2 versus 2.3 x 10(-8)) was highly significant (P = 0.0009). Both mutant frequency and adduct level were highest in the 16 most heavily exposed workers. Overall, a significant increase of mutant frequency was observed with adduct level (P = 0.008) as well as with age (P < 0.0001). The age dependence was higher in the GSTM1-negative slow acetylators (3.1%/year) as compared to the three other genotype combinations (2.4-2.5%/year). There was no significant difference in mutant frequency or in adduct level between the GSTM1-negative (49.3% of the population) and positive individuals, or between the slow (60.9% of the population) and rapid acetylators. Among the slow acetylators, however, a significantly higher adduct level (P = 0.03) was obtained for the GSTM1-negative individuals as compared to the GSTM1-positive individuals. These results suggest a possible role of both GST mu and NAT2 for individual susceptibility to carcinogen exposure.