Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification capacity in the rat
Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification capacity in the rat
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DOI：
10.1016/s0278-6915(03)00122-4
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发表时间：
2003-10-01
影响因子：
4.3
通讯作者：
Dragsted, LO
中科院分区：
文献类型：
--
作者：
Breinholt, VM;Molck, AM;Dragsted, LO
在雄性F344大鼠上，研究了长期给予中、高剂量(1-100 mg/kg饲料)抗氧化剂、番茄红素、栎素和白藜芦醇或番茄红素和槲皮素混合物的潜在的有利或不利影响。对血液、肝脏和结肠中的毒性和防御机制的选定标记物进行了分析，并评估了抗氧化剂给药对肝脏和结肠中可能的癌前病变的影响。膳食致癌物质2-氨基-3-甲基咪唑[4，5-f]喹啉(IQ)(200 mg/kg膳食)作为促氧化剂、遗传毒性和一般毒性控制。智商可使大鼠血浆蛋白质和DNA氧化产物水平、肝脏谷胱甘肽S转移酶阳性灶面积和结肠异常隐窝灶数目增加。所有抗氧化剂和抗氧化剂组合显著增加淋巴细胞DNA损伤水平，其程度与智商诱导的效果相当。与未检测到GST-P病灶的对照组不同，在接触栎素、番茄红素以及两者联合作用的动物中，GST-P病灶被检测到。但GST-P灶体积的增加无统计学意义。结果表明，中、高剂量的常见抗氧化剂对实验动物的淋巴细胞DNA有损伤作用，并可引起低水平的癌前病变。因此，长期接触中到高剂量的抗氧化剂可能通过促氧化机制和非氧化机制调节癌症的发生。(C)2003爱思唯尔有限公司。保留所有权利。
The potential beneficial or adverse affect of prolonged dietary administration of moderate to high doses (1-100 mg/kg diet) of the antioxidants, lycopene, quercetin and resveratrol or a mixture of lycopene and quercetin was investigated in male F344 rats. Selected markers for toxicity and defense mechanisms were assayed in blood, liver and colon and the impact of the antioxidant administrations on putative preneoplastic changes in liver and colon was assessed. The dietary carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) (200 mg/kg diet) served as a pro-oxidant, genotoxicity and general toxicity control. IQ increased the levels of protein and DNA oxidation products in plasma, the area of glutathione S-transferase-placental form positive (GST-P) foci in the liver as well as the number of colonic aberrant crypt foci (ACF). All antioxidants and the antioxidant combination significantly increased the level of lymphocytic DNA damage, to an extent comparable with the effect induced by IQ. In contrast to the control group where no GST-P foci were detected, GST-P foci were detected in animals exposed to quercetin, lycopene and the combination of the two. However, the increase in the volume of GST-P foci did not reach statistical significance. The present results indicate that moderate to high doses of common dietary antioxidants can damage lymphocyte DNA and induce low levels of preneoplastic liver lesions in experimental animals. Long-term exposure to moderate to high doses of antioxidants may thus via pro-oxidative mechanisms and non-oxidative mechanisms modulate carcinogenesis. (C) 2003 Elsevier Ltd. All rights reserved.