Correlation between biomarkers of human exposure to genotoxins with focus on carcinogen-DNA adducts

Abstract

Correlations among biomarkers, an important issue in biomarker research, provide enhanced insight and understanding of the complexity of molecular mechanisms initiated by environmental genotoxic agents in the human organism. Occupational and environmental exposures mostly represent mixtures of genotoxic agents, whereas the specificity of biomarker measurements varies widely. Here, we give an overview of the correlation studies with particular emphasis on DNA adduct biomarker analysis of exposure to polycyclic aromatic hydrocarbons (PAHs) and/or tobacco smoke. We have collected data on correlations between different DNA adduct detection methods, DNA adduct structures and DNA adduct levels in human tissues. Data are also presented on the correlation between DNA adducts and other biomarkers of exposure and of early biological effects, including protein adducts, urinary metabolites and cytogenetic end points. In numerous studies, 32P-postlabelling and immunoassay measurements of DNA adducts recognized the difference between exposure groups similarly; however, at the individual level, there was, in general, not a statistically significant correlation between the two determinations. Inconsistency was found regarding the correlation between the levels of total bulky adducts and specific single DNA adduct structures. A number of studies found a positive correlation between DNA adduct levels in target and surrogate tissues, although stratification for exposure level may have influenced the results. Characteristically, there was a positive correlation between DNA adduct levels in tumour and normal tissue pairs. In general, there was a lack of correlation between DNA adducts and urinary PAH metabolites, but after stratification for particular genetic polymorphisms correlation may have emerged between the two biomarkers of exposure. The correlations with cytogenetic biomarkers were very complex, with examples of both positive correlation and lack of correlation. Exploration of correlations among biomarkers contributes to the further progress of molecular cancer epidemiology and to the selection of the optimal biomarkers for the investigation of human exposure to carcinogens.

Bulky DNA adducts and breast cancer risk in the prospective EPIC-Italy study

“…32 P-postlabelling and immunoassays are the most widely used methods for the detection of carcinogen-DNA adducts. At a certain level, these two methods are not comparable due to only partial overlapping of their substrate specificities [34]. The 32 P-postlabelling method has the advantage of high sensitivity for bulky DNA adducts typically formed from aromatic compounds [16,34,35], but is not suitable for the identification of specific DNA adduct structures.…”

Biological monitoring of carcinogens: current status and perspectives

“…Current exposures to carcinogens are estimated by measuring either the chemical itself or its metabolite(s) in body Xuids (Angerer et al 2007;Brandt and Watson 2003;Weisel 2010) and short-term cumulative exposures through the detection of lymphocyte DNA and blood protein adducts (GyorVy et al 2008, Godschalk et al 2003Ricceri et al 2010). However, these measurements represent snapshots that are not necessarily representative of relevant exposures, and they can only be compared with reference values and exposure limits, when available.…”

“…Assessing the eVects Several markers of biological eVect, including chromosomal aberrations (Sram et al 2007;Mahata et al 2004;DeMarini 2004), micronuclei formation (GyorVy et al 2008, Bonassi et al 2003Bolognesi et al 2011;Fenech et al 2011a, b), telomere shortening (Pavanello et al 2010;Pavanello et al 2011) and speciWc mutations (Vähäkangas 2003;Carton et al 2007) have been proposed to assess cancer risk. However, only few studies were designed prospectively, among which none was linked to a given exposure.…”

“…In summary, although several biochemical/biological biomarkers have been proposed to detect early eVects of carcinogens, the complexity of carcinogenetic processes makes it almost impossible to appreciate their place within the natural history of disease. Further consideration should also be given to the necessity of measuring such biomarkers in accessible tissues-usually blood components, especially leucocytes-and consequently to the uncertain relationship with the corresponding changes in target organs (GyorVy et al 2008). Whereas only a few studies, mainly on DNA adducts, addressed this question (Wiencke et al 1995(Wiencke et al , 1999GyorVy et al 2004;Peluso et al 2004;Ally et al 2009), one should recognize that the access of chemicals to cells and the repairing capabilities and turnover of cells diVer across tissues.…”

Avaliação citogenética e molecular de trabalhadores intoxicados pelo benzeno

“…Os biomarcadores de exposição podem ser medidos em diferentes tecidos, inclusive no sangue, e a partir dessa análise pode-se estimar a dose biológica efetiva em um organismo, pois somente uma parte da quantidade total da substância química absorvida atingirá o tecido-alvo (Jakubowski et al, 2005;Gyorffy et al, 2008).…”