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

据估计，饮食因素在导致人类癌症的原因中所占比例最大（35%）。我们发现维生素A（视黄醇）及其衍生物（视网膜）在HL-60细胞中引起细胞DNA的分裂，并显著诱导8-氧- 7,8 -二氢-2'-脱氧鸟苷（8-oxodG）的形成，而在H_2O_2抗性的HP100细胞中则没有，提示H_2O_2参与其中。类维生素a自氧化过程中超氧化物的生成与8-oxodG的形成显著相关。视黄醇和视网膜具有促氧化能力，这可能导致β-胡萝卜素补充剂的致癌作用（J. Biol）。化学275,2003,2000)。像西兰花和花椰菜这样的蔬菜含有大量的异硫氰酸酯，异硫氰酸酯被认为是很有前途的人类癌症化学预防剂。然而，我们发现异硫氰酸酯通过生成超氧化物显著诱导8-oxodG的形成，这是由异硫氰酸酯（自由基）生成SH基团产生的。生物……更多。医学杂志，28,797,2000)。DNA加合物的形成被认为是致癌芳胺导致DNA损伤的主要原因。我们研究了几种芳香胺和n -羟基代谢物引起DNA氧化损伤的能力。4-氨基联苯（4-ABP）自由基的n -羟基代谢物。医学杂志。医学，30,765-773,2001)，杂环胺PhIP（致癌作用）和氨基苯基诺哈曼（突变）。Res. 494, 63-72, 2001)被发现引起Cu（II）介导的DNA损伤，添加内源性还原剂NADH可显著增强这一过程。我们得出结论，除了DNA加合物的形成外，DNA氧化损伤可能在这些芳香胺的致癌过程中起重要作用。食品添加剂溴酸钾（KBrO_3）可诱导大鼠肾细胞肿瘤。我们发现KBrO_3诱导了8-oxodG的形成。我们推测GSH和Cys等SH化合物对KBrO_3的还原产生溴氧化物和溴自由基，这是引起鸟嘌呤氧化的活性物质，导致KBrO_3肾癌(Chem。毒理学杂志，14,678-685,2001)。少

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