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A comparison of covalent DNA binding of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in respiratory tissues from human, rat and mouse.
Stoner GD; Schut HA; Daniel FB; Dixit R
Cancer Lett 1986 Mar; 30(3):231-241
The covalent DNA binding of benzo(a)pyrene (50328) (BaP) and 7,12- dimethylbenz(a)anthracene (57976) (DMBA) was studied in mammalian respiratory tissues. The purpose of the study was to investigate the difference in tumorigenicity of BaP and DMBA. Male A/J-mice were injected intraperitoneally with 150 milligrams per kilogram tritium labeled BaP or DMBA. The animals were killed 4, 12, 24 or 48 hours post injection, the liver and lungs were removed, and DNA was isolated and assayed for BaP or DMBA/DNA adducts. Explants from human bronchus and peripheral lung, A/J-mouse peripheral lung, and tracheal tissue from Fischer-344-rats were incubated with tritium labeled BaP or DMBA. The extent of covalent binding to the tissue DNA was determined. Patterns of BaP/DNA and DMBA/DNA adduct formation were investigated by high performance liquid chromatography. In-vivo, binding of BaP or DMBA to DNA in the liver was higher than in the lungs at all time points. BaP binding increased with time after exposure, but leveled off after 24 hours. DMBA/DNA binding was maximal at 48 hours and was higher than that of BaP at this time. In-vitro, covalent binding of DMBA to DNA of mouse lung and rat trachea was similar and was significantly higher than that of BaP. Binding of BaP and DMBA was similar in both human tissues and did not differ from BaP binding in the rodent tissues. The patterns of BaP/DNA and DMBA/DNA adduct formation in respiratory tissues were similar in all three species. The authors conclude that the higher susceptibility of mouse lung and rat trachea to DMBA as compared to BaP may be related to the greater covalent binding of DMBA to DNA. Both BaP and DMBA pose a risk for human lung cancer. This risk may be equal for both compounds.
NIOSH-Author; Toxic-materials; Respiratory-irritants; Biological-effects; Chemical-binding; Laboratory-animals; Cancer-rates; Lung-function; Tissue-disorders; Liver-function
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