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DOSE RELATED DIFFERENCES IN DNA ADDUCT LEVELS IN RODENT TISSUES FOLLOWING SKIN APPLICATIONS OF COMPLEX MIXTURES FROM AIR POLLUTION SOURCES
Citation:
Gallagher, J., M. Jackson, M.H. George, AND J. Lewtas. DOSE RELATED DIFFERENCES IN DNA ADDUCT LEVELS IN RODENT TISSUES FOLLOWING SKIN APPLICATIONS OF COMPLEX MIXTURES FROM AIR POLLUTION SOURCES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-90/037 (NTIS PB90217571), 1990.
Description:
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 C57 mice following multiple topical treatments ranging from (1-120) mg per mouse. articulate 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. ositive and negative control animals were treated with either 1.2 mg Benzo(a)Pyrene or acetone alone. NA was isolated from skin, lung and liver DNA 4 hours following the last application and analyzed for DNA adducts using the nuclease P1 version of the 32P-post labeling assay. ach of the particulate extracts produced distinct patterns of DNA adducts. road diagonal radioactive zone (DRZ) presumably, representing multiple DNA adducts, was observed for coke oven, coal soot and diesel modified DNA samples. ne 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. his adduct was detected in all tissues examined and represented approximately 12-34 percent of the total number of adducts detected within the DRZ for all coke oven and smoky coal exposed tissues (skin, lung and liver). n contrast, this adduct represented 49-69 percent of the total radioactivity quantitated in the lung diesel modified DNA samples. he highest total number of adducts resulted from the metabolism of coke oven extract followed by smoky coal and diesel treatments respectively. ose-dependent increase in adduct formation was observed for all tissues in the diesel and smoky coal treated mice. iver and lung DNA adduct levels increased in a dose dependent manner in the coal soot and coke oven treated mice. n contrast, no consistent dose-response relationship was observed in the skin DNA samples isolated from the coke oven modified DNA samples. he percentage of dose administered detected as DNA adducts increased in all tissues as the dose decreased for all three complex mixtures. hese data have important implications for low dose risk assessment of these complex mixtures.