Cytotoxicity, DNA fragmentation and sister-chromatid exchange in Chinese hamster ovary cells exposed to the lipid peroxidation product 4-hydroxynonenal and homologous aldehydes.
The cytotoxic and genotoxic activities of 4-hydroxypentenal (HPE), 4-hydroxyhexenal (HHE), 4-hydroxyoctenal (HOE), 4-hydroxynonenal (HNE) and 4-hydroxyundecenal (HUE) were investigated in Chinese hamster ovary (CHO) cells. All five 4-hydroxyalkenals reduced plating efficiency in a concentration (ranging from 7 to 170 microM) lower than that producing a parallel reduction of trypan blue-excluding cells, but with both methods the increase in molarity needed to obtain a lethal effect was constantly rather small. With all five 4-hydroxyalkenals a significant amount of DNA fragmentation, as revealed either by the alkaline elution assay or by alkaline denaturation followed by chromatographic partition of single- and double-stranded DNA, was detected only after cell exposure to a cytotoxic concentration. HPE, HHE and HOE induced a clear-cut increase of sister-chromatid exchange (SCE) frequency, while that displayed by cells treated with HNE and HUE was minimal, even if dose-dependent and statistically significant. Since 4-hydroxyalkenals have been shown to originate from biomembrane lipids peroxidation, these findings should be taken into consideration in the assessment of the genotoxic role of lipoperoxidation in humans.
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004277:DNA, Single-Stranded / Q000032:analysis*; D005260:Female; D008054:Lipid Peroxides / Q000633:toxicity; D009153:Mutagens; D009691:Nucleic Acid Denaturation; D010053:Ovary; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000447:Aldehydes; D004277:DNA, Single-Stranded; D008054:Lipid Peroxides; D009153:Mutagens; C027576:4-hydroxy-2-nonenal