Surh Y J, Park K K, Miller J A
McArdle Laboratory for Cancer Research, School of Medicine, University of Wisconsin, Madison 53706.
Carcinogenesis. 1994 May;15(5):917-20. doi: 10.1093/carcin/15.5.917.
6-Sulfooxymethylbenzo[a]pyrene has recently been shown to be a strong hepatocarcinogen in infant male B6C3F1 mice (Y.-J.Surh et al., Biochem. Biophys. Res. Commun., 172, 85-91, 1990) and appears to be an ultimate carcinogenic metabolite of 6-hydroxymethylbenzo[a]pyrene and possibly of benzo[a]pyrene. It produced high levels of aralkyl DNA adducts in the livers of B6C3F1 mice and also exhibited strong direct mutagenicity toward Salmonella typhimurium TA98 without metabolic activation. In the present study we found that ascorbic acid significantly reduced the bacterial mutagenicity and in vitro covalent DNA binding of 6-sulfooxymethylbenzo[a]pyrene. Ascorbic acid forms a mutagenically inactive covalent adduct with 6-sulfooxymethylbenzo[a]pyrene, which appears to account for its novel protective mechanism against this reactive sulfuric acid ester. It seems likely that the formation of this adduct involves aralkylation of an ascorbic acid anion by a presumed carbo cation derived from the electrophilic sulfuric acid ester.
6-磺氧基甲基苯并[a]芘最近已被证明是雄性B6C3F1幼鼠中的一种强致癌物（Y.-J. Surh等人，《生物化学与生物物理学研究通讯》，172，85 - 91，1990），并且似乎是6-羟甲基苯并[a]芘以及可能是苯并[a]芘的最终致癌代谢产物。它在B6C3F1小鼠肝脏中产生高水平的芳烷基DNA加合物，并且在没有代谢激活的情况下对鼠伤寒沙门氏菌TA98也表现出很强的直接致突变性。在本研究中，我们发现抗坏血酸显著降低了6-磺氧基甲基苯并[a]芘的细菌致突变性和体外共价DNA结合。抗坏血酸与6-磺氧基甲基苯并[a]芘形成一种无致突变活性的共价加合物，这似乎解释了其针对这种活性硫酸酯的新保护机制。这种加合物的形成似乎涉及抗坏血酸阴离子被一种源自亲电硫酸酯的假定碳阳离子进行芳烷基化反应。
