Aromatic DNA adducts, micronuclei and genetic polymorphism for CYP1A1 and GST1 in chimney sweeps.
Aromatic DNA adducts in total white blood cells, cytochrome P450 (CYP) class 1A1 and glutathione transferase (GST1) class mu genotypes and micronuclei in T- and B-lymphocytes were studied in 69 full-time chimney sweeps and 35 controls, all male subjects. The sweeps had a higher (22%) but statistically non-significant increase in the level of DNA adducts as compared to the controls when all individuals independent of genotype were compared. The non-inducible CYP1A1 genotype, m1/m1, lacking a MspI restriction site at the 3' end of the gene, was associated with significantly higher adduct levels in the sweeps. Among the 26 sweeps with the combined genotype m1/m1 and GST1(-), a statistically significant 60% increase in median adduct levels was observed as compared with those 14 control subjects with the corresponding genotype. Smoking also showed a significant effect on the level of adducts. The effect on DNA adducts by sweeping, smoking and genotype appeared to be additive and independent of each other. DNA adducts in sweeps were moderately but statistically significantly correlated with micronuclei in both T- and B-lymphocytes. The correlation between adduct levels and micronuclei was most marked in T-lymphocytes of individuals lacking the GST1 gene.
Unit of Molecular Epidemiology, Karolinska Institute, Huddinge, Sweden.
M
M
Ichiba
L
L
Hagmar
A
A
Rannug
B
B
Högstedt
A K
AK
Alexandrie
U
U
Carstensen
K
K
Hemminki
D000328:Adult; D000368:Aged; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000378:metabolism*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D011083:Polycyclic Compounds / Q000378:metabolism*; D011110:Polymorphism, Genetic
D007527:Isoenzymes; D011083:Polycyclic Compounds; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase