CYTOTOXIC AND GENOTOXIC EFFECTS OF 4-HYDROXYNONENAL IN CEREBRAL ENDOTHELIAL-CELLS

Oxygen free radicals are produced in the central nervous system (CNS) as a consequence of normal physiological metabolic reactions of neuron al cells, but there is evidence accumulating that they are also implic ated in the processes leading to a number of pathological changes in t he brain, A general mechanism whereby oxygen free radicals induce tiss ue damage is lipid peroxidation (LPO), which generates a large variety of water-soluble carbonyl compounds, Due to their high reactivity, we focused our investigations on 4-hydroxyalkenals, in particular on 4-h ydroxynonenal (HNE), the major 4-hydroxyalkenal. Two phenotypes of cer ebral endothelial cells (cECs) were treated with various concentration s of 4-hydroxynonenal and the cyto- and genotoxic effects studied. The cytogenetic endpoints determined were chromosomal aberrations and the induction of micronuclei. Three hours of incubation with HNE induced significantly elevated levels of chromosomal aberrations at concentrat ions greater than or equal to 1 mu M and micronuclei at concentrations greater than or equal to 10 mu M in both cEC phenotypes, compared to the controls, Cytotoxicity was observed at a concentration of 50 mu M HNE and was significantly higher in the elongated and spindle-shaped c EC phenotype (type II) than in the epithelial cEC phenotype (type I), The results indicate that cECs are affected by HNE even at low concent rations with minor differences between the two cEC phenotypes. (C) 199 7 Elsevier Science B.V.