Implication of Superoxide Radical Anion in Promotion of Neoplastic Transformation in Mouse JB6 Cells by TPA

Specific biochemical and genetic events that appear to be essential to promotion of transformation in JB6 cells have been identified.1 The two earliest events appear to be the activation of protein kinase C (PKC) (and the subsequent phosphorylation of its substrates) and an increase in oxidant stress. There is a significant body of evidence that implicates reactive oxygen, and the superoxide radical anion in particular, as an important mediator of tumor promotion.2 This evidence includes studies with nonphorbol tumor promoters as well as TPA, several tissues invivo, and a number of different model systems invitro. For example, copper(II)(3,5-diisopropylsalicylate)₂ (CuDIPS) is a potent inhibitor of phorbol ester-mediated tumor promotion in the epidermis of CD-I mice.3 CuDIPS is a lipophilic copper complex that catalyzes the dismutation of the superoxide anion radical at a rate similar to that of SOD, its biological counterpart Invivo.4 In invitro studies with JB6 P+ cells, SOD was observed to inhibit promotion of transformation by TPA. Other invitro studies have demonstrated that SOD will inhibit TPA-dependent radiogenic transformation of C3H10T1/2 cells.5,6