GSTMI and NAT2 genotypes and urinary mutagens in coke oven workers

The influence of the metabolic genotypes GSTMI and NAT2 on theurinary excretion of mutagens in 46 coke oven workers (27 ofthem smokers) was studied. Exposure to polycyclic aromatic hydrocarbons(PAH) was estimated from urinary 1-pyrenol levels, which variedfrom 0.23 to 5.59 µmol/mol creatinine. Fourteen urinesamples (30.4%), all but one belonging to smokers, were positivefor mutagenic activity (i.e. at least one of the assayed doseswas able to double the number of spontaneous revertants). Nineof the urine-positive subjects were both GSTMI-null and NAT2-ss(64.3%), while the same combination of genotypes was found innine out of 31 urine-negative subjects (29.0%) (P < 0.05).Significantly more smoking workers with the genotype combinationGSTM1-null/NAT2-ss showed positive urine mutagenicity than theother subjects (75.0 versus 28.6%, P< 0.05). Smokers withthe slow acetylator genotype showed a significantly higher frequencyof positive urine samples than smoking fast acetylators (64.7versus 22.2%, P < 0.05). Our results suggest that smokingcoke oven workers with genotypes unfavourable for detoxificationof aromatic amines (NAT2-ss) and PAH (GSTM1-null) may have anincreased risk of developing bladder cancer.