Chromosomal aberrations in humans induced by urban air pollution: influence of DNA repair and polymorphisms of glutathione S-transferase M1 and N-acetyltransferase 2.
We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes as a biomarker of genotoxic damage and dimethylsulfate-induced unscheduled DNA synthesis in mononuclear WBCs, the glutathione S-transferase M1 (GSTM1) genotype, and the N-acetyltransferase 2 (NAT2) genotype as biomarkers of susceptibility. The bus drivers, who had previously been observed to have elevated levels of aromatic DNA adducts in their peripheral mononuclear cells, showed a significantly higher frequency of cells with chromosomal aberrations as compared with the postal workers. In the bus drivers, unscheduled DNA synthesis correlated negatively with the number of cells with gaps, indicating a protective effect of DNA repair toward chromosome damage. Bus drivers with the GSTM1 null and slow acetylator NAT2 genotype had an increased frequency of cells with chromosomal aberrations. NAT2 slow acetylators also showed elevated chromosomal aberration counts among the postal workers. Our results suggest that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations.
Knudsen
L E
LE
National Institute of Occupational Health, Copenhagen, Denmark.
Norppa
H
H
Gamborg
M O
MO
Nielsen
P S
PS
Okkels
H
H
Soll-Johanning
H
H
Raffn
E
E
Järventaus
H
H
Autrup
H
H
D000328:Adult; D000397:Air Pollution / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002869:Chromosome Aberrations; D004260:DNA Repair / Q000502:physiology*; D003718:Denmark; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D005819:Genetic Markers; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D016012:Poisson Distribution; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014505:Urban Population
D001191:Arylamine N-Acetyltransferase; D015415:Biomarkers; D005819:Genetic Markers; D005982:Glutathione Transferase