Investigation of a possible role for superoxide anion production in tumour promotion.

Abstract

The effect of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on superoxide (O-.2) production and superoxide dismutase (SOD) levels has been investigated in human leukocytes and human and rodent fibroblast cell lines. Both O-.2 production and a lowering of the SOD levels were observed in the human leukocytes, but these changes could not be correlated with the induction of gross chromosomal aberrations by TPA. Similarly the use of an O-.2-generating system failed to induce chromosome aberrations. However, a small percentage increase in chromosome aberrations was observed in human fibroblasts after repeated and prolonged exposure to TPA. TPA was shown to reduce the SOD levels in these cells. Overall however, the data suggest that the chromosomes are not the primary site of action for the superoxide anions produced by TPA.