DNA adducts and related biomarkers in populations exposed to environmental carcinogens

Abstract

Prevention of environmentally related cancer will be enhanced by the availability of sensitive early warning systems and by improvements in quantitative assessment of human risks. Accordingly, we have carried out a series of molecular epidemiologic studies aimed at validating a panel of biologic markers, including carcinogen–DNA and –protein adducts, sister chromatid exchange, micronucleus formation, DNA strand breaks, and DNA repair capacity. Results from three such studies illustrate the usefulness of these biomarkers in elucidating low-dose–response relationships, correlations between biomarkers, and the range of variation in biomarkers between individuals exposed to similar concentrations of carcinogens. Low-level workplace or ambient exposures to styrene, ethylene oxide, and polycyclic aromatic hydrocarbons (PAH) were associated with significant increases in both molecular dose of carcinogens (adducts) and various markers of preclinical effects. Correlations between biomarkers varied by exposure. For example, in the styrene study, sister chromatid exchange frequency was not correlated with any of the markers, in contrast to the studies of ethylene oxide and PAH. Significant molecular effects were observed not only in occupationally exposed people but also in residents of an area in Poland characterized by high levels of air pollution. For example, the mean PAH–DNA level in exposed residents (winter sample) was 30.4 adducts per 108 nucleotides. This level was significantly higher than that of adducts seen in summer samples from the same area (4.2/108), or in winter samples from residents of a rural area (11.01/108). Significant seasonal variation in PAH–DNA adduct formation in this group was consistent with recorded fluctuations in air pollution levels. Striking interindividual variation was observed in all three exposed populations.

DNA adduct burden and tobacco carcinogenesis

“…Several studies have reported statistically significant variations in DNA adduct levels according to the season of study Grzybowska et al, 1993;Moller et al, 1996;Motykiewicz et al, 1998;Palli et al, 2001;Perera et al, 1992;Tang et al, 1995;Topinka et al, 2000). Many of these reported higher 'background' adduct levels in winter compared with summer, and these variations appear to be related to the airborne concentrations of PAHs and nitro-PAHs, particularly for studies carried out in industrialized and polluted areas of Poland and the Czech Republic (Moller et al, 1996;Topinka et al, 2000).…”

Path Analysis of Biomarkers of Exposure and Early Biological Effects among Coke-Oven Workers Exposed to Polycyclic Aromatic Hydrocarbons

“…In molecular epidemiology studies, biological effects are more frequently measured by biomarkers, which are divided into three categories: measures of internal dose, early biological response, and host susceptibility (6,7). Many studies have found the associations between PAH environmental exposure, whose internal dose is usually quantified by 1-hydroxypyrene (1-OHP) in urine, and an increase in the levels of carcinogen-DNA adducts, sister chromatid exchange, and chromosomal aberrations (8)(9)(10)(11)(12). In addition, environmental exposure interacts intricately with environmental responsive genes and some known behavioral factors such as tobacco smoking and alcohol consumption (13)(14)(15).…”

Polycyclic Aromatic Hydrocarbon Levels and Mutagenic Activities of Organic Extracts from Airborne Particles in Santiago de Chile

“…PAHs in the atmosphere are known to be predominantly associ ated with particulate matter. The risk to human health from PAHs is due to their multi-source and presence in multi-pollutant mixtures which might contain not only a great variety of hydrocarbons but also derivatives such as the nitroarenes [4], Epidemiological evidence, though inconclusive, points to urban air pollution as a possible contributory agent in respiratory cancers [5,6] as well as in other diseases such as bronchitis and emphysema.…”