Metabolism of 4-hydroxynonenal, a cytotoxic lipid peroxidation product, in Ehrlich mouse ascites cells at different proliferation stages.

ABSTRACT

The aldehydic lipid peroxidation product 4-hydroxynonenal (HNE) is cytotoxic at high concentrations (in the range of 100 microM); at low concentrations, it disturbs cell proliferation and exhibits genotoxic effects, and in the submicromolar range, HNE is chemotactic and stimulates phospholipase C. HNE is rapidly metabolized in eukaryotic cells. Here the metabolism of HNE was studied in suspensions of Ehrlich mouse ascites cells at different periods of the tumor age. The main products of HNE which were identified in the Ehrlich ascites cells, were glutathione-HNE-conjugate, hydroxynonenoic acid, and 1,4-dihydroxynonene. The formation of glutathione conjugates following the addition of HNE was higher in early phase cells when compared with cells in the late phase of tumor growth. That was in accordance with the increased consumption of the reduced form of glutathione. Ehrlich ascites tumor cells at the proliferation phase were able to reduce a higher amount of exogenous-added HNE, compared with cells at the stationary phase.