Dose-Related Differences in DNA Adduct Levels in Rodent Tissues Following Skin Application of Complex Mixtures from Air Pollution Sources

摘要

Dose-related differences in the binding of DNA reactive intermediates for three environmentally important complex particulate extracts and a well studied carcinogen Benzo(a)Pyrene (B(a)P) were examined in female C-57 mice following multiple topical treatments ranging from (1-120) mg per mouse. Particulate extracts from coke oven, coal soot and diesel exhaust were selected as model complex mixtures based on short term mutagenicity assays, animal bioassays for carcinogenicity or epidemiological studies where increased incidences of lung cancer in exposed populations were detected. Positive and negative control animals were treated with either 1.2 mg Benzo(a)Pyrene or acetone alone. DNA was isolated from skin, lung and liver DNA 24 hours following the last application and analyzed for DNA adducts using the nuclease P1 version of the 32p-postlabeling assay. Each of the particulate extracts produced distinct patterns of DNA adducts. A broad diagonal radioactive zone (DRZ) presumably representing multiple DNA adducts, was observed for coke oven, coal soot and diesel modified DNA samples. One adduct, common to all three complex mixture modified DNA samples, comigrated with the major B(a)P adduct observed following treatment with B(a)P alone. These data have important implications for low dose risk assessment of these complex mixtures. (Copyright (c) Oxford University Press.)