Journal Article

Oxidative stress promotes the development of transformation: involvement of a potent mutagenic lipid peroxidation product, acrolein

Wakako Takabe, Etsuo Niki, Koji Uchida, Satoshi Yamada, Kimihiko Satoh and Noriko Noguchi

in Carcinogenesis

Volume 22, issue 6, pages 935-941
Published in print June 2001 | ISSN: 0143-3334
Published online June 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.6.935
Oxidative stress promotes the development of transformation: involvement of a potent mutagenic lipid peroxidation product, acrolein

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The effect of intracellular oxidative stress on the development of cell transformation was studied. Mouse embryo C3H/10T1/2 fibroblasts pre-treated with benzo[a] pyrene, developed transformed foci on exposure to free radical generators, such as 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) and 3-morpholinosydnonimine hydrochloride (SIN-1). These compounds generate peroxyl radicals and peroxynitrite, respectively. Neither AAPH nor SIN-1 alone induced transformation. The level of intracellular antioxidants, such as α-tocopherol and glutathione (GSH), decreased with time of exposure to the free radical generators, whereas the addition of exogenous α-tocopherol, GSH and ebselen showed a reduction in the frequency of transformation. An early event during exposure to AAPH and SIN-1 was the generation of acrolein, a highly mutagenic lipid peroxidation product, which was suppressed by the addition of α-tocopherol. Furthermore, it was confirmed that acrolein induced the transformation of cells which were pre-treated with benzo[a]pyrene but not of the untreated cells. These results suggest that acrolein may act as an important mediator of cell transformation under oxidative stress.

Keywords: AAPH, 2,2′-azobis(amidinopropane) dihydrochloride; BP, bensol[a]pyrene; D-MEM, Dulbecco's modified Eagle medium; DMSO, dimethyl sulfoxide; D-PBS, Dulbecco's-phosphate buffered saline; FBS, fetal bovine serum; FDP-lysine, Nε-(3-formyl-3,4-dehydropiperidino) lysine; GSH, glutathione; H2O2, hydrogen peroxide; HNE, 4-hydroxy-2-nonenal; HO• , hydroxyl radical; 1O2, singlet oxygen; O2• –, superoxide; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; PMA, phorbol 12-myristate 13-acetate; RNS, reactive nitrogen species; ROS, reactive oxygen species; SIN-1, 3-morpholinosydnonimine hydrochloride; SOD, superoxide dismutase; SOS, sodium 1-octansulfonate.

Journal Article.  4758 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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