GSTM1 AND NAT2 GENOTYPES AND URINARY MUTAGENS IN COKE-OVEN WORKERS

The influence of the metabolic genotypes GSTM1 and NAT2 on the urinary excretion of mutagens in 46 coke oven workers (27 of them smokers) wa s studied, Exposure to polycyclic aromatic hydrocarbons (PAH) was esti mated from urinary 1-pyrenol levels, which varied from 0.23 to 5.59 mu mol/mol creatinine, Fourteen urine samples (30.4%), all but one belon ging to smokers, were positive for mutagenic activity (i.e. at least o ne of the assayed doses was able to double the number of spontaneous r evertants), Nine of the urine-positive subjects were both GSTM1-null a nd NAT2-ss (64.3 %), while the same combination of genotypes was found in nine out of 31 urine-negative subjects (29.0 %) (P < 0.05). Signif icantly more smoking workers with the genotype combination GSTM1-null/ NAT2-ss showed positive urine mutagenicity than the other subjects (75 .0 versus 28.6 %, P < 0.05), Smokers with the slow acetylator genotype showed a significantly higher frequency of positive urine samples tha n smoking fast acetylators (64.7 versus 22.2 %, P < 0.05). Our results suggest that smoking coke oven workers with genotypes unfavourable fo r detoxification of aromatic amines (NAT2-ss) and PAH (GSTM1-null) may have an increased risk of developing bladder cancer.