Differential influence of the lipid peroxidation product 4-hydroxynonenal on the growth of human lymphatic leukaemia cells and human periopherial blood lymphocytes.
The purpose of this study was to compare the influence of physiological and supraphysiological concentrations of 4-hydroxynonenal (HNE), a peroxidation product of omega-6-polyunsaturated fatty acids, on the proliferation of malignant CEM-NKR lymphatic leukaemia cells and normal human lymphocytes (HPBM). Furthermore the growth modulating effect of phytohemagglutinin (PHA) on both cell lines was examined. The effects of HNE were monitored 18 hours and 3 days after incubation, using two different DNA-synthesis assays ([3H]-thymidine- and BrdU- incorporation) and a mitochondrial dehydrogenases activity assay (MTT). On the one hand HNE showed dose-dependent effects on both of the cell lines, while on the other hand a clear difference between the response of CEM-NKR cells and HPBM cells, respectively, to HNE was observed. On CDM-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 with the physiological concentration of HNE. Furthermore the presence of PHA in the culture medium increased the difference of the response of CEM-NKR and HPBM cells, respectively to HNE.
Semlitsch
Thomas
T
Institute of Molecular Biology, Biochemistry and Microbiology, University of Graz, Austria.
Tillian
H Manfred
HM
Zarkovic
Neven
N
Borovic
Suzana
S
Purtscher
Martin
M
Hohenwarter
Otmar
O
Schaur
Rudolf J
RJ
D000447:Aldehydes / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D000447:Aldehydes; D006131:Growth Inhibitors; D010835:Phytohemagglutinins; D014316:Tritium; D001973:Bromodeoxyuridine; C027576:4-hydroxy-2-nonenal; D013936:Thymidine