Environmental air pollution and DNA adducts in Copenhagen bus drivers—Effect of GSTM1 and NAT2 genotypes on adduct levels

Abstract

The lymphocyte bulky PAH-DNA adduct levels have been studied in persons occupationally exposed to ambient air pollution. The exposure group consisted of 90 healthy, nonsmoking bus drivers from the Copenhagen area, divided into three exposure groups according to driving area, and 60 rural controls (smokers and non-smokers). PAH-DNA adducts were determined by 32P-postlabelling with the butanol enrichment procedure. The bus drivers answered a comprehensive questionnaire on passive smoking, residential area, diet and other potential confounding variables. A significantly higher adduct level was observed in bus drivers working in central Copenhagen (1.214 fmol/microg DNA, n = 49) compared with both those driving in the dormitory (median: 0.507 fmol/microg DNA, P = 0.046, n = 16) and suburban (median: 0.585 fmol/microg DNA, P = 0.041, n = 25) areas. All three groups had higher adduct levels than rural controls (0.074 fmol/microg DNA, n = 60, P< 0.001). No significant influence on adduct levels was demonstrated from potential confounders, including smoking and diet. The effect of the metabolizing enzymes, GSTM1 and NAT2, on adduct levels was investigated. No statistically significant effects were observed on adduct levels from GSTM1 or NAT2, either individually or combined, but a non-significant trend was seen for individuals with GSTM1*0/0 (null), since they had higher adduct levels in all exposure groups. This study demonstrated that lymphocyte PAH-DNA adduct levels were related to levels of exposure to urban air pollution and indicated that these adducts might be helpful as a means of classifying better different exposure groups for epidemiological studies. Furthermore, it demonstrated the ability of 32P-postlabelling to discern small differences in low exposure to ambient air pollution and suggested a possible effect of GSTM1*0/0 on DNA adduct levels.

Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress.

“…An alternative explanation is that highly modified albumin from highly exposed bus drivers could easily be recognized by proteases and degraded. In animal (12). In this study, the negative correlation between albumin and bulky carcinogen-DNA adduct level seen in the combined group was only statistically significant in the GSTM1 null group.…”

“…A large interindividual variation in the biomarker levels could be seen. A significant higher level of bulky carcinogen-DNA adducts (12) was observed in the group dassified as the high exposure group, whereas the levels of PAH-albumin adduct and markers of oxidative stress, MDA and AAS, in hemoglobin were significantly higher in the suburban/semirural group. The level of the biomarkers in the postal worker group was similar to the levels in the suburban/semirural bus driver group (Table 1).…”

“…Transportation workers have an increased exposure to carcinogenic PAHs, e.g., truck drivers (29). Increased exposure to genotoxic compounds have been reported in bus drivers in Copenhagen using the 32P-postlabeling method to measure bulky carcinogen-DNA adducts (12). Drivers who spent most of their working hours in central Copenhagen had a higher adduct level than suburban and semirural drivers.…”

“…The 32P-postlabeling method has been used extensively to detect bulky carcinogen-DNA adducts in peripheral lymphocytes from occupationally exposed people and people living in areas with different levels of ambient air pollution (9)(10)(11)). An increased level of adducts has been observed in nonsmoking bus drivers working in the center of Copenhagen (12). A result of primary damage to DNA is gene mutation or chromosomal mutations, e.g., aberrations.…”

DNA adduct levels and DNA repair polymorphisms in traffic-exposed workers and a general population sample

“…5,6 Several studies have reported higher levels of DNA adducts among subjects heavily exposed to air pollutants, such as police officers, bus drivers, news vendors and residents in heavily polluted areas. [7][8][9] A recent meta-analysis of 13 32 P-DNA postlabeling studies on occupational cohorts has shown that the association between DNA adducts and air pollution exposure is significant in heavily exposed industrial workers and in less severely exposed urban workers. 10 Bulky DNA adducts, such as those induced by PAH, may be repaired by base excision repair (BER) and nucleotide excision repair (NER) pathways.…”