engleski

Differential influence of the signalling aldehyde 4-hydroxynonenal, a mediator of oxidative stress, on growth of human lymphatic leukemia cells and human peripheral blood lymphocytes

The purpose of htis study was to compare influence of physiological and supraphysiological concentrations of the signalling aldehyde 4-hydroxynonenal (HNE), a peroxidation product of omega-6-polyunsaturated fatty acids and mediator of oxidative stress, on the proliferation of CEM-NKR, a human lymphoid cell line of the T lineage that is resistant to the activity of natural killer cells, and normal lymphocytes (HPBM). Furthermore the growth modulating effect of phytohemaglutinin (PHA) on both cell lines was examined. The effects of HNE were monitored 18 hours and 3 days after incubation in vitro, using two different DNA-synthesis assays (3H-thymidine and BrdU- incorporation) and a mitochondrial dehydrogenase activity assay (MTT). One the one hand HNE showed dose-dependent effects on both cell lines, on the other hand a clear difference betweeen the response of CEM-NKR cells and HPBM cells respectively to HNE was observed. On CEM-NKR cells both concentrations of HNE caused significant cytotoxic effects on DNA-synthesis as well as on mitochondrial activity, while in contrast, HNE did not show any significant toxicity to HPBM cells. After 3 days there was even a slight stimulation of DNA-synthesis in presence of the physiological concentration of HNE. Furthermore the addition of PHA to the culture medium potentiated the difference of the response of CEM-NKR and HPBM cells, resp. to HNE. These results raise the question whether other tumor cells react also differently to HNE in comparison to their counterpart normal cells. That would increase our knowledge about the bases of cancer development and the possible use of mediators of oxidative stress in cancer therapy.

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