| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Dietary factor is estimated to have the largest proportion (35 %) in the causation of human cancer. We revealed that vitamin A (retinol) and its derivative (retinal) caused cellular DNA cleavage and significantly induced 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) formation in HL-60 cells but not in H_2O_2 -resistant HP100 cells, suggesting the involvement of H_2O_2. The superoxide generation during autoxidation of retinoids was significantly correlated with the formation of 8-oxodG. Retinol and retinal have prooxidant abilities, which might lead to carcinogenesis of the supplements of β-carotene (J. Biol. Chem. 275, 2003, 2000). Vegetables like broccoli and cauliflower contain substantial quantities of isothiocyanates, and isothiocyanates were proposed as promising chemopreventive agents for human cancers. However, we revealed that isothiocyanates significantly induced 8-oxodG formation through generation of superoxide by the yield of SH group from isothiocyanates (Free Radic. Biol
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. Med. 28, 797, 2000). DNA adduct formation is thought to be a major cause of DNA damage by carcinogenic aromatic amines. We investigated the ability of several aromatic amines and N-hydroxy metabolite to cause oxidative DNA damage. The N-hydroxy metabolites of 4-aminobiphenyl (4-ABP) (Free Radic. Biol. Med. 30, 765-773, 2001), heterocyclic amines PhIP (Carcinogenesis in press) and aminophenylnorharman (Mutat. Res. 494, 63-72, 2001) were found to cause Cu(II)-mediated DNA damage, and addition of the endogenous reductant NADH led to dramatic enhancement of this process. We conclude that, in addition to DNA adduct formation, oxidative DNA damage may play an important role in the carcinogenic process of these aromatic amines. Potassium bromate (KBrO_3), a food additive, induces renal-cell tumors in rats. We showed that KBrO_3 induced 8-oxodG formation. We speculated that reduction of KBrO_3 by SH compounds like GSH and Cys yields bromine oxides and bromine radicals, which are the reactive species that cause guanine oxidation, leading to renal carcinogenesis of KBrO_3 (Chem. Res. Toxicol. 14, 678-685, 2001). Less
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