Preferential oxidation of cell surface sialic acid by periodate leads to promotion of transformation in JB6 cells

Abstract

Tumor promoters such as phorbol esters and benzoyl peroxide are free radical generators which produce elevation of reactive oxygen. Tumor promoters also produce a decrease in trisialoganglioside (GT) synthesis in JB6 clonal cell lines that are sensitive to promotion of neoplastic transformation but not in resistant variants. This communication describes a study designed to test the hypothesis that the 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive ganglioside GT is a target molecule for TPA-induced oxidation and that this GT oxidation leads via reduced GT synthesis to promotion of neoplastic transformation. Direct oxidation of JB6 cellular GT by sodium metaperiodate (NaIO4) led to both decreased GT synthesis as measured by [14C]glucosamine incorporation and promotion of anchorage independent transformation, thus providing support for the hypothesis. Further support came from the observation that promotion of transformation by NaIO4, like TPA, was specifically inhibited by added GT. Neither oxidized GT nor other gangliosides inhibited NaIO4 promotion. Promotion of neoplastic transformation in JB6 cells by NaIO4 may share at least one event with TPA promotion, namely, oxidation of cell surface trisialoganglioside.