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 g enotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 1 01 postal workers in the Copenhagen metropolitan area, We used the frequenc y 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 sig nificantly higher frequency of cells with chromosomal aberrations as compar ed with the postal workers, In the bus drivers, unscheduled DNA synthesis c orrelated negatively with the number of cells with gaps, indicating a prote ctive effect of DNA repair toward chromosome damage, Bus drivers with the G STM1 null and slow acetylator NAT2 genotype had an increased frequency of c ells with chromosomal aberrations. NAT2 slow acetylators also showed elevat ed chromosomal aberration counts among the postal workers, Our results sugg est that long-term exposure to urban air pollution (,vith traffic as the ma in contributor) induces chromosome damage in human somatic cells. Low DNA r epair capacity and GSTM1 and NAT2 variants associated with reduced detoxifi cation ability increase susceptibility to such damage, The effect of the GS TM1 genotype, which was observed only in the bus drivers, appears to be ass ociated with air pollution, whereas the NAT2 genotype effect, which affecte d all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations.