Sawa T, Akaike T, Kida K, Fukushima Y, Takagi K, Maeda H
Department of Microbiology, Kumamoto University School of Medicine, Japan.
Cancer Epidemiol Biomarkers Prev. 1998 Nov;7(11):1007-12.
A diet high in fat and iron is known as a risk factor in cancer epidemiology. However, the details of the molecular mechanism remains to be elucidated. We examined the possible implication of lipid peroxyl radicals generated from fatty acids and heme-iron in DNA damage, and hence in the possibility of colon cancer. F344 female rats were given N-nitroso-N-methylurea six times during a 2-week period and then fed diets containing different amounts of safflower oil and hemoglobin (rich in iron) for 36 weeks; the occurrence of colon cancer was determined by H&E staining. In this animal model, simultaneous feeding of a fat diet and heme-iron produced a significant increase (P < 0.05) in the incidence of colon cancer compared with a diet without hemoglobin. Electron paramagnetic resonance and chemiluminescence studies revealed that oxidized refined vegetable oils, particularly safflower oil, readily generated lipid peroxyl radicals in the presence of various heme compounds, and the peroxyl radicals did effectively cleave DNA. Unpurified native vegetable oils contain a high amount of peroxyl radical scavengers, whereas conventional refining processes seem to reduce the levels of many valuable anti-peroxyl radical compounds abundant in plant seeds. In conclusion, lipid peroxides and heme components generate peroxyl radical species that exert DNA-cleaving activity. A plausible explanation is that lipid peroxyl radicals thus generated, which originated from routine dietary components such as fat and red meat, may contribute, at least in part, to the high incidence of colon cancer.
在癌症流行病学中，高脂肪和高铁饮食被认为是一个风险因素。然而，其分子机制的细节仍有待阐明。我们研究了脂肪酸和血红素铁产生的脂质过氧自由基在DNA损伤中的可能作用，以及由此引发结肠癌的可能性。在2周内给F344雌性大鼠6次注射N-亚硝基-N-甲基脲，然后给它们喂食含有不同量红花油和血红蛋白（富含铁）的饲料36周；通过苏木精-伊红染色确定结肠癌的发生情况。在这个动物模型中，与不含血红蛋白的饲料相比，同时喂食高脂肪饲料和血红素铁显著增加了（P < 0.05）结肠癌的发病率。电子顺磁共振和化学发光研究表明，氧化精炼植物油，特别是红花油，在各种血红素化合物存在的情况下容易产生脂质过氧自由基，并且这些过氧自由基确实能有效切割DNA。未提纯的天然植物油含有大量的过氧自由基清除剂，而传统的精炼过程似乎降低了植物种子中大量存在的许多有价值的抗过氧自由基化合物的含量。总之，脂质过氧化物和血红素成分会产生具有DNA切割活性的过氧自由基。一个合理的解释是，由此产生的脂质过氧自由基源自脂肪和红肉等日常饮食成分，可能至少部分地导致了结肠癌的高发病率。
