Lipid peroxidation products and clastogenic material in culture media of human leukocytes exposed to the tumor promoter phorbol-myristate-acetate

Abstract

The chromosome-damaging effect of PMA in blood cultures is mediated by secondary products which are formed by the cells in response to the interaction with this tumor promoter. Since this effect could be influenced by antioxidant enzymes and by inhibitors of arachidonic acid metabolism, the present study was undertaken in order to determine whether the formation of these clastogenic substances is concomitant with the formation of AA metabolites and other lipid peroxidation products. Besides the clastogenic effect of ethyl-acetate extracts, the similarities of cytogenetic and biochemical results (conjugated dienes and TBA-reactive material) obtained for the influence of other blood cells than lymphocytes in the culture system, the importance of PHA stimulation and the protective effect of antioxidant enzymes were arguments in favour of a causal relationship between chromosome damage and lipid peroxidation (enzymatic or nonenzymatic). If AA release from membrane phospholipids was prevented by inhibition of phospholipase A₂, neither conjugated dienes nor TBA-reactive material were found, and chromosome damage was reduced considerably. However, the results obtained with inhibitors of the cyclo- and lipoxygenase pathway were not conclusive, and discrepancies were also observed in the time course of appearance of clastogenic material and lipid peroxidation products.