INHIBITORY EFFECT OF VITAMIN-C ON THE MUTAGENICITY AND COVALENT DNA-BINDING OF THE ELECTROPHILIC AND CARCINOGENIC METABOLITE, 6-SULFOOXYMETHYLBENZO[A]PYRENE

6-Sulfooxymethylbenzo[a]pyrene has recently been shown to be a strong hepatocarcinogen in infant male B6C3F(1) mice (Y.-J.Surh et al., Bioch em. Biophys. Res. Commun., 172, 85-91, 1990) and appears to be an ulti mate carcinogenic metabolite of 6-hydroxymethylbenzo[a] pyrene and pos sibly of benzo[a]pyrene and 6-methylbenzo[a]pyrene. It produced high l evels of aralkyl DNA adducts in the livers of B6C3F(1) mice and also e xhibited strong direct mutagenicity toward Salmonella typhimurium TA98 without metabolic activation. In the present study we found that asco rbic acid significantly reduced the bacterial mutagenicity and in vitr o covalent DNA binding of 6-sulfooxymethylbenzo[a]pyrene. Ascorbic aci d forms a mutagenically inactive covalent adduct with 6-sulfooxymethyl benzo[a]pyrene, which appears to account for its novel protective mech anism 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 sulfu ric acid ester.