32P-postlabeling analysis of DNA adducts in tissues of rats exposed to coke-oven emissions

Abstract

Coke-oven workers are occupationally exposed to emissions containing relatively high levels of polycyclic aromatic hydrocarbons. Epidemiological studies suggest that this occupational exposure may lead to an increased risk of lung cancer. To evaluate a biologically effective exposure dose in human biomonitoring studies DNA carcinogen adduct analysis is frequently used. The most readily available source of cellular DNA in these studies is white blood cells (WBC). It is questionable whether WBC are an appropriate surrogate for target tissue cells. In this study an animal model was used to examine the relationship between DNA adduct levels in target tissues and WBC as a surrogate. Rats were exposed to emissions on the top of a coke-oven battery for 24 h during simultaneous sampling of the air for chemical analysis of polycyclic aromatic hydrocarbons. 32P-Postlabeling analysis of DNA adducts in lung, heart, liver and WBC with the butanol enrichment procedure was conducted. DNA adduct profiles differ in target and non-target tissues and WBC analyzed. One major adduct was detected in the DNA from all tissues and WBC analyzed that exhibited the same chromatographic mobility as the predominant B(a)P adduct of the standard DNA sample. The highest levels of this adduct were observed in DNA from lung and heart — 16.3 and 12.9 adducts/10 9 nucleotides. The elevation compared to local control animals was 6.8-fold for lung, 8.6-fold for heart, in WBC DNA 3-fold and in liver DNA only 2-fold. In DNA samples from WBC and heart mainly this major adduct was observed. In liver DNA the other four distinct spots outside the diagonal zone (DRZ) and in lung two faster-migrating adducts inside the DRZ with higher intensities were detected. Evaluating total DNA adduct levels, almost the same extent of DNA damage in lung, heart and liver was observed (46.8, 37.7 and 46.2 adducts/10 9 nucleotides; WBC only 6.7 adducts/10 9 nucleotides). Our data showed that DNA injury in target tissue cells caused by exposure to coke-oven emissions may be more significant than expected only according to DNA adduct levels in WBC.