Oxidative stress-regulated gene expression and promotion of morphological transformation induced in C3H/10T1/2 cells by ammonium metavanadate.
Promoters of C3H/10T1/2 cell morphological transformation that elevate intracellular oxidant levels can be distinguished by a spectrum of induced gene expression, which includes the oxidant-responsive murine proliferin gene family. Proliferin transcripts were induced 40- to 100-fold by 20 microM ammonium metavanadate, 20-fold by 5 microM vanadium pentoxide but only three-fold by vanadium oxide sulfate. Consistent with its response to other oxidant chemicals, induction of proliferin by ammonium metavanadate was inhibited almost completely by the antioxidant N-acetylcysteine (8 mM). Ammonium metavanadate (5 microM), added as promoter in two-stage morphological transformation assays, amplified yields of Type II and Type III foci in monolayers of 20-methylcholanthrene-initiated C3H/10T1/2 cells. Ammonium metavanadate also induced formation of Type II foci in single-step transformation assays. The results suggest that pentavalent vanadium compounds could promote morphological transformation in C3H/10T1/2 cells by creating a cellular state of oxidative stress, sufficient to induce elevated expression of the proliferin gene family.
Parfett
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Mutagenesis Section, Environmental Health Directorate, Health Canada, Ottawa, Ontario.
Pilon
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001345:Autoradiography; D015152:Blotting, Northern; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D003720:Densitometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006133:Growth Substances / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011388:Prolactin; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014638:Vanadates / Q000378:metabolism / Q000633:toxicity*; D001613:beta 2-Microglobulin / Q000235:genetics
D000975:Antioxidants; D018076:DNA, Complementary; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C000634106:Prl2c2 protein, mouse; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D014638:Vanadates; D011388:Prolactin