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KMID : 0366919940060010029
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Sungkyun Pharmceutical Journal
1994 Volume.6 No. 1 p.29 ~ p.35
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Formation and Persistence of BPDE-I-protein Adduct in Sprague-Dawley rats and ICR mice Exposed to Benzo(a)pyrene
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Abstract
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Chemical carcinogens are metabolically activated to reactive intermediates which bind covalently to cellular macromolecules(DNA, RNA and protein) and the extent of binding seems to be correlated with the carcinogenic potency of carcinogens. Especially, carcinogen-DNA adduct is believed to be the critical marker in chemical carcinogenesis. Also, protein adducts have been suggested as a surrogate marker for DNA adducts at the target site since the proteins are more readily available in human monitoring studies and the relationship between DNA and protein adducts has been well demonstrated in many studies.
In this study, we have compared the formation and persistence of BPDE-I (benzo(a)pyrene 7, 8-dihydrodil-9, 10-epoxide-I, ultimate carcinogenic form of benzo(a)pyrene)-protein adduct in various tissues(liver, lung, kidney, spleen and stomach) of ICR mice and Sprague-Dawley(S.D.) rats following oral and i.p. treatment with benzo(a)pyrene(B[a]P, 500 mg/kg). BPDE-I-protein adducts were quantitated by ELISA(enzyme linked immunosorbent assay) using monoclonal antibody 8E11.
In orally and i.p. treated S.D. rats, the highest level of BPDE-I-protein adduct was observed in the liver, kidney and stomach. But in ICR mice, the higher level of BPDE-I-protein adduct was observed in the lung(78.63 fmol/ugprotein) and stomach(70.85 fmol/ug protein) after oral administration of B[a]P. After i.p. treatment of B[a]P in ICR mice, higher levels of BPDE-I-protein adduct was found in the lung and kidney. The persistence of BPDE-I-protein adduct was found in the liver of S.D. rats and in the lung, kidney, and stomach of ICR mice.
These results indicate that there is no species correlation in the formation and persistence of BPDE-I-protein adduct between S.D. rats and ICR mice. However, the difference of protein adduct patterns between ICR mice and S.D. rats may reflect species differences in metabolic and detoxification pathways. These data also clearly demonstrate that protein adduct persistence may be affected by protein turn over and possibly repair, which has been only accepted in DNA.
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