Analysis of the human DNA damage by dietary factors via reactive oxygen species and cancer prevention

饮食因素通过活性氧对人类 DNA 损伤的分析与癌症预防

基本信息

批准号：
12670318
负责人：
MURATA Mariko
金额：
$ 1.92万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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 … More . 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

饮食因素估计在人类癌症的原因中具有最大的比例（35％）。我们揭示了维生素A（视黄醇）及其衍生物（视网膜）引起细胞DNA裂解，并显着诱导HL-60细胞中的8-氧-7、8-二氢-2'-氧鸟苷（8-oveodg）形成，但在H_2O_2-2O_2-2O_2-resistant hp100细胞中却不是hp100 cells in__2。类视视视感素期间的超氧化物产生与8-氧化物的形成显着相关。视黄醇和视网膜具有证明能力，这可能导致β-胡萝卜素补充剂的癌变（J. Biol。Chem。275，2003，2000）。西兰花和花椰菜等蔬菜中含有大量异硫氰酸盐，并提出异硫氰酸酯作为人类癌症的有希望的化学预防剂。但是，我们揭示了异硫氰酸盐会显着诱导。 8-氧化物通过异硫氰酸盐的SH组产生产生的超氧化物形成（自由放射性生物……更多。Med。28，797，2000）。 DNA加合物的形成被认为是致癌芳香胺DNA损伤的主要原因。我们研究了几种芳香胺和N-羟基代谢产物引起氧化DNA损伤的能力。 4-氨基苯基（4- aBP）的N-羟基代谢物（自由放射性Bric。Biol。30，765-773，2001），杂环胺PHIP（媒体中的致癌作用）和氨基苯基norharman和amophenylnorharman（mutat。内源性减少的NADH导致了这一过程的显着增强。我们包括，除了DNA添加剂形成外，氧化DNA损伤在这些芳香族性失忆的致癌过程中可能起重要作用。溴酸钾（KBRO_3），一种食物添加剂，诱导大鼠的肾细胞肿瘤。我们表明KBRO_3诱导了8-OXODG的形成。我们推测，诸如GSH和CYS之类的SH化合物减少KBRO_3会产生溴氧化物和溴自由基，它们是引起鸟嘌呤氧化的反应性物种，导致KBRO_3的肾脏致癌作用（Chem。Toxicol。14，678-685，2001）。较少的