Journal Article

Tumor promotion by hydrogen peroxide in rat liver epithelial cells

Ruo-Pan Huang, Ao Peng, Mohammad Z. Hossain, Yan Fan, Ajit Jagdale and Alton L. Boynton

in Carcinogenesis

Volume 20, issue 3, pages 485-492
Published in print March 1999 | ISSN: 0143-3334
Published online March 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.3.485
Tumor promotion by hydrogen peroxide in rat liver epithelial cells

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Reactive oxygen species, including H2O2, play an important role in the tumor promotion process. Using an in vitro model of tumor promotion involving the rat liver epithelial oval cell line T51B, the tumor promoting activity of H2O2 in N-methyl-N′-nitro-N-nitrosoguanidine-initiated cells was studied. In this assay system, the promoting effect of H2O2 is evidenced by the formation of colonies in soft agar, appearance of foci in monolayer culture, disruption of gap junction communication (GJC) in foci areas and growth at higher saturation densities. H2O2 preferentially induced the expression of c-fos, c-jun, c-myc and egr-1, while JunB and JunD levels remained almost unchanged. H2O2 also induced hyperphosphorylation of Cx43 and disruption of GJC. The effects of H2O2 on tumor promotion, induction of immediate early (IE) genes and disruption of GJC are blocked by antioxidants. These results suggest that H2O2 acts as a tumor promoter in rat liver non-neoplastic epithelial cells and that the induction of IE genes and disruption of GJC are two possible targets of H2O2 during the tumor promotion process.

Keywords: DMF, dimethyl formamide; EGF, epidermal growth factor; GJC, gap junction communication; IE, immediate early; MNNG, N-methyl-N′-nitro-N-nitrosoguanidine; NAC, N-acetylcysteine; OA, okadaic acid; ROS, reactive oxygen species; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TPA, 12-O-tetradecanoylphorbol-13-acetate.

Journal Article.  6526 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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