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) was studied. Exposure to polycyclic aromatic hydrocarbons (PAH) was estimated from urinary 1-pyrenol levels, which varied from 0.23 to 5.59 micromol/mol creatinine. Fourteen urine samples (30.4%), all but one belonging to smokers, were positive for mutagenic activity (i.e. at least one of the assayed doses was able to double the number of spontaneous revertants). Nine of the urine-positive subjects were both GSTM1-null and 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). Significantly 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 than smoking fast acetylators (64.7 versus 22.2%, P < 0.05). Our results suggest that smoking coke oven workers with genotypes unfavourable for detoxification of aromatic amines (NAT2-ss) and PAH (GSTM1-null) may have an increased risk of developing bladder cancer.
Gabbani
G
G
Institute of Occupational Health, University of Padova, Italy.
Hou
S M
SM
Nardini
B
B
Marchioro
M
M
Lambert
B
B
Clonfero
E
E
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001483:Base Sequence; D003077:Coke / Q000633:toxicity*; D017931:DNA Primers; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009153:Mutagens / Q000378:metabolism*; D016273:Occupational Exposure; D011721:Pyrenes / Q000378:metabolism*; D012907:Smoking; D016482:Urinalysis
D003077:Coke; D017931:DNA Primers; D009153:Mutagens; D011721:Pyrenes; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D005982:Glutathione Transferase; C033146:1-hydroxypyrene