Role of catalase and oxidative stress in hepatic peroxisome proliferator-induced morphological transformation of Syrian hamster embryo cells.
Several hepatic peroxisome proliferators (HHPs) such as di(2-ethylhexyl)phthalate (DEHP), mono(2-ethylhexyl)-phthalate, clofibrate and tiadenol, induce morphological transformation of Syrian hamster embryo (SHE) cells in vitro. According to one hypothesis, the hepatocarcinogenic effect of HPPs is caused by an oxidative stress due to increased H2O2-production from the strongly induced peroxisomal beta-oxidation of fatty acids. Thus, increased transformation frequencies by HPPs should be obtained when catalase was inhibited by 3-amino-1,2,4-triazole (amitrole). However, co-exposure to HPPs and amitrole did not enhance the transformation frequencies for any of the HPPs. The sensitivity of SHE cells for oxidative agents was studied by using menadione and H2O2. Menadione only induced transformation at a toxic concentration, while H2O2 induced transformation at non-toxic concentrations. To study the generation of oxidative radicals in SHE cells, electron spin resonance was employed. No oxidative radical formation was detected in tiadenol- or DEHP-exposed SHE cells. When menadione or H2O2 were added during the measurements, oxidative radicals were found. A transmission electron microscopic study showed a small number of peroxisomes, and did not reveal any increase in the number of peroxisomes in clofibrate-treated SHE cells.
Mikalsen
S O
SO
Laboratory for Environmental and Occupational Cancer, Institute for Cancer Research, Norwegian Radium Hospital, Oslo.
Kaalhus
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O
Reith
A
A
Sanner
T
T
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors / Q000502:physiology*; D002461:Cell Line, Transformed / Q000166:cytology / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D002994:Clofibrate / Q000494:pharmacology*; D006224:Cricetinae; D004051:Diethylhexyl Phthalate / Q000494:pharmacology* / Q000031:analogs & derivatives; D004578:Electron Spin Resonance Spectroscopy; D005233:Fatty Alcohols / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D008647:Mesocricetus / Q000196:embryology*; D008830:Microbodies / Q000502:physiology*; D014812:Vitamin K / Q000494:pharmacology
D005233:Fatty Alcohols; D014812:Vitamin K; C004568:tiadenol; D006861:Hydrogen Peroxide; D004051:Diethylhexyl Phthalate; D002374:Catalase; C016599:mono-(2-ethylhexyl)phthalate; D002994:Clofibrate; D000640:Amitrole