Biomarker Studies in Northern Bohemia

Abstract

Studies were conducted in northern Bohemia to simultaneously evaluate personal exposures to air pollution in the form of respirable particles containing polycyclic aromatic hydrocarbons (PAHs) and biomarkers of exposure, biological effective dose, genetic effects, and metabolic susceptibility. The series of biomarkers included PAH metabolites in urine, urine mutagenicity, PAH-DNA adducts in white blood cells determined by32P-postlabeling, PAH-albumin adducts determined by enzyme-linked immunosorbent assay (ELISA), DNA damage in lymphocytes detected by comet assay, chromosomal aberrations, sister chromatid exchanges, and glutathione S-transferase Ml (GSTM1) genotypes. For these studies, a group of women who work outdoors about 30% of their daily time was selected. In a pilot study, a group of women from a polluted area of the Teplice district (northern Bohemia) was compared with a group of women from a control district of southern Bohemia (Prachatice). In a follow-up repeated-measures study, a group of nonsmoking women from Teplice was sampled repeatedly during the winter season of 1993 to 1994. Personal exposure monitoring for respirable particles (<2.5 pm) was conducted for the 24-hr period before collection of blood and urine. Particle extracts were analyzed for carcinogenic PAHs. In the pilot study and in the follow-up study, a highly significant correlation between individual personal exposures to PAHs and DNA adducts was found (r= 0.54, p= 0.016; r= 0.710, p< 0.001, respectively). The comet parameter (percentage DNA in tail; %T) correlated with exposures to respirable particles (r=0.304, p=0.015). The GSTM1 genotype had a significant effect on urinary PAH metabolites, urine mutagenicity, and comet parameters (%T and tail moment) when the GSTM1 genotype was considered as a single factor affecting these biomarkers. Multifactor analysis of variance considering exposure and adjusting the data for GSTM1, age, and diet showed that the effect of personal exposures to PAHs on the variability of biomarkers (DNA adducts, comet parameters, urine mutagenicity) might be higher than the effect of the GSTM1 genotype. These results show the importance of considering all potential factors that may affect the biomarkers being analyzed. Environ Health Perspect 104(Suppl 3):591-597 (1996)

Influence of GSTM1 genotypes on anti -BPDE-DNA adduct levels in mononuclear white blood cells of humans exposed to PAH

“…The eect of genetically determined dierences in detoxifying enzymes, mostly GSTM1, on DNA adduct levels derived from environmental and occupational exposure to PAH has formed part of several recent studies (for a review, see Sram [53]). In general, no association has been found between GSTM1 (*0/*0 or active) and DNA adducts in white blood cells of subjects environmentally exposed to PAH [3,37], smokers [21,36], coal-tar-treated patients [51], bus maintenance workers [25], bus drivers [38], chimney sweeps [26], and coke-oven workers [4]. However, in agreement with our results, in a very recent study the clear-cut eect of GSTM1, and even of CYP1A1 genotypes [48], on BPDE-DNA adduct formation in white blood cells (WBC) of coke-oven workers was found using the HPLC/¯uorescence method.…”

The relationship between biomarkers of oxidative DNA damage, polycyclic aromatic hydrocarbon DNA adducts, antioxidant status and genetic susceptibility following exposure to environmental air pollution in humans

“…Examples include DNA samples from bus drivers in Copenhagen [4], and from populations living in regions with increased pollution in Czech Republic [5] and [6], and Poland [7]. In contrast to this, other studies have not shown a similar relationship.…”

Genotoxic risk assessment in white blood cells of occupationally exposed workers before and after alteration of the polycyclic aromatic hydrocarbon (PAH) profile in the production material: comparison with PAH air and urinary metabolite levels

“…The DNA adduct formation induced by some PAHs does not appear to be the only mechanism that leads to cancer formation. At this stage, there is little information describing the levels of strand breaks and of oxidized bases in DNA from workers exposed to PAHs (Binkova et al 1996;Carstensen et al 1999;Popp et al 1997). Previously published results (Marczynski et al 2002) indicate that PAH exposure creates oxidative DNA damage, as measured by the production of one type of oxidative base modification, the 8-oxodGuo, and the production of DNA strand beaks and alkali-labile sites.…”