S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
The strong hepatocarcinogenicity of the electrophilic and mutagenic metabolite 6-sulfooxymethylbenzo[α]pyrene and its formation of benzylic dna adducts in the livers of infant male B6C3F1 mice
- Surh, Young-Joon; Liem, Amy; Miller, Elizabeth C.; Miller, James A.
- Issue Date
- Biochemical and Biophysical Research Communications, Vol.172 No.1, pp.85-91
- 6-Hydroxymethylbenzo[α]pyrene was activated to an electrophilic and mutagenic sulfuric acid ester metabolite by rat and mouse liver sulfotransferase activity. The intrinsic mutagenicity of this reactive ester, 6-sulfooxymethylbenzo[α]pyrene, was inhibited by glutathione and glutathione S-transferase. A single i.p. dose of 2.5 nmol/g body wt of 6-sulfooxymethylbenzo[α]pyrene in infant male B6C3F1 mice induced liver tumors in 35 of 36 mice at 10 months with an average multiplicity of 4.4. A comparable dose of the parent hydrocarbon, 6-hydroxymethylbenzo[α]pyrene, was only a tenth as active. The electrophilic sulfuric acid ester produced high levels of benzylic DNA adducts in the livers of these mice that accounted for about 80% of the total DNA adducts. These results strongly suggest that this sulfuric acid ester is an important ultimate electrophilic and carcinogenic metabolite in carcinogenesis by 6-hydroxymethylbenzo[α]pyrene and possibly even by 6-methylbenzo[α]pyrene and benzo[α]pyrene in mouse liver. © 1990 Academic Press, Inc.
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