STIMULATION OF HELA-CELL GROWTH BY PHYSIOLOGICAL CONCENTRATIONS OF 4-HYDROXYNONENAL

The aim of this study was to analyze the growth response of HeLa cells over a prolonged period of time to a single exposure of physiological and supraphysiological concentrations of 4-hydroxynonenal (HNE), a pe roxidation product of omega-6-polyunsaturated fatty acids. Furthermore , the growth modulating effect of serum factors, particularly albumin, on the growth pattern was examined. The effects of HNE on the growth rate and viability of the cells, as well as on the incorporation of la belled amino acids were monitored daily over a period of four days. Fe tal calf serum not only had a growth stimulating effect but also modul ated the action of HNE. In neither respect was albumin able to substit ute for serum indicating that the influence of serum was not exerted v ia an albumin-HNE conjugate. HNE had a clear dose-dependent effect and a distinction could be made between a supraphysiological concentratio n (100 mu M), which was primarily cytotoxic and a physiological range (below 10 mu M) which showed growth modulatory effects. These effects consisted of a transient inhibition in the initial phase of the cell g rowth, which under optimal conditions (in presence of serum) was follo wed by a period of increased proliferation, compared to untreated cont rol cultures, until confluence was attained. It is suggested that HNE is not only a toxic product of lipid peroxidation, but a physiological growth regulating factor as well.