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Carcinogenesis, Vol. 22, No. 6, 935-941, June 2001
© 2001 Oxford University Press

CARCINOGENESIS

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

Wakako Takabe, Etsuo Niki, Koji Uchida1,, Satoshi Yamada2,, Kimihiko Satoh3, and Noriko Noguchi4,

Research Center for Advanced Science and Technology, The University of Tokyo, Komaba, Meguro, Tokyo 153-8904,
1 Laboratory of Food and Biodynamics, Nagoya University Graduate School of Bioagricultural Sciences, Nagoya 464-8601,
2 Tsukuba Research Laboratory, NOF Co., Tsukuba 300-2635,
3 Second Department of Biochemistry, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan

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 {alpha}-tocopherol and glutathione (GSH), decreased with time of exposure to the free radical generators, whereas the addition of exogenous {alpha}-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 {alpha}-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.


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