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

Tumor promoters such as phorbol esters and benzoyl peroxideare free radical generators which produce elevation of reactiveoxygen. Tumor promoters also produce a decrease in trisialoganglioside(G_T) synthesis in JB6 clonal cell lines that are sensitive topromotion of neoplastic transformation but not in resistantvariants. This communication describes a study designed to testthe hypothesis that the 12-O-tetra-decanoylphorbol-13-acetate(TPA)-responsive ganglioside G_T is a target molecule for TPA-inducedoxidation and that this G_T oxidation leads via reduced G_T synthesisto promotion of neoplastic transformation. Direct oxidationof JB6 cellular G_T by sodium metaperiodate (NaIO₄) led to bothdecreased G_T synthesis as measured by [¹⁴C]glucosamine incorporationand promotion of anchorage independent transformation, thusproviding support for the hypothesis. Further support came fromthe observation that promotion of transformation by NaIO₄ likeTPA, was specifically inhibited by added G_T. Neither oxidizedG_T nor other gangliosides inhibited NaIO₄ promotion. Promotionof neoplastic transformation in JB6 cells by NaIO₄ may shareat least one event with TPA promotion, namely, oxidation ofcell surface trisialoganglioside.