title: THE SENSITIVITY OF CELLS WITH THE VARIOUS LEVEL OF NAD(P)H:QUINONE OXIDOREDUCTASE 1 TO CYTOTOXIC ACTION OF QUINONIMINES AND α-TOCOPHEROL SYNTHETIC DERIVATIVES.
abstract: The effects of α-tocopherol with shortened to 6 carbon atoms side chain (α-Toc-C6), α-tocopherol succinate (α-TS) and quinonimine 2,6-dichlorophenolindophenol (DCPIP) on DT-diaphorase activity and viability of rat thymocytes, splenocytes and hepatocytes were investigated. It was shown that the lowest basal activity of the enzyme is inherent in splenocytes. In comparison to splenocytes, DT-diaphorase activity was 1.4 and 5 times higher in thymocytes and hepatocytes, respectively. It was found that the sensitivity of cells to the cytotoxic effect of DCPIP was inversely proportional to the basal level of DT-diaphorase activity and accompanied by its activation with subsequent inhibition at non-toxic and toxic concentrations, respectively. Hepatocytes were least sensitive to the cytotoxic effect of α-Toc-C6. In thymocytes and splenocytes α-Toc-C6 exerts inhibitory effects on DT-diaphorase, whereas in hepatocytes an increased activity of the enzyme was observed, which probably caused their high survival rate. Simultaneous induction of cytochrome P450 enzyme expression by α-Toc-C6 in hepatocytes is also possible. Cytotoxic effect of α-TS does not depend on the basal level of DT-diaphorase activity in cells, is not accompanied by its induction and it is most likely determined by the non-specific esterase activity.
authors.forename: G V
authors.initials: GV
authors.lastname: Petrova
authors.forename: A V
authors.initials: AV
authors.lastname: Parshykov
mesh_terms: D015086:2,6-Dichloroindophenol / Q000633:toxicity; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity*; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007097:Imines / Q000633:toxicity*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009928:Organ Specificity; D061251:Primary Cell Culture; D011809:Quinones / Q000633:toxicity*; D051381:Rats; D060168:Thymocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D024502:alpha-Tocopherol / Q000031:analogs & derivatives / Q000633:toxicity*
chemical_list: D003603:Cytotoxins; D007097:Imines; D011809:Quinones; D015086:2,6-Dichloroindophenol; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D024502:alpha-Tocopherol