Flavonoids modulate Comet assay responses to food mutagens in human lymphocytes and sperm
Flavonoids modulate Comet assay responses to food mutagens in human lymphocytes and sperm
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DOI：
10.1016/s0027-5107(97)00306-0
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发表时间：
1998-06-18
影响因子：
2.3
通讯作者：
Yu, TW
中科院分区：
文献类型：
--
作者：
Anderson, D;Dobrzynska, MM;Yu, TW
类黄酮、水飞蓟素、杨梅素、槲皮素、山奈酚、芦丁和山奈酚-3-芸香苷已与食品诱变剂 3-氨基-1-甲基-5H-吡啶并 (4,3-b) 吲哚 (Trp-P-2) 和 2-氨基-3-甲基咪唑-(4,5-f) 喹啉一起进行了检查(IQ)，在来自供体 A 的人类淋巴细胞和来自供体 B 的人类精子的彗星测定中。这些化合物本身已被证明在彗星测定中产生阳性反应，食物诱变剂也是如此。然而，当与食物诱变剂结合使用时，黄酮类化合物会产生抗原毒性作用，因为彗星试验中淋巴细胞和精子中的 DNA 损伤减少。这些测定是在没有代谢激活的情况下进行的，因为当在代谢激活的血液中检查槲皮素和山奈酚时，与没有代谢激活的情况下获得的反应几乎没有或没有差异。在血液中，最低剂量的类黄酮反应会加剧或协同作用。在精子中，水飞蓟素、杨梅素和槲皮素仅观察到抗原毒性作用，而山奈酚通常没有保护作用。除了 Trp-P-2 和 IQ 之外，还仅在供体 A 和 C 的人淋巴细胞中对食物诱变剂 2-氨基-1-甲基-6-苯基咪唑并 (4,5-b) 吡啶 (PhIP) 与水飞蓟素和杨梅素进行了联合检测。在低剂量的这些黄酮类化合物中也发现了类似的效应加剧，而在高剂量时则具有抗原毒性作用。这在艾姆斯测试中得到了证实。淋巴细胞和精子的情况略有不同，但在相似的剂量范围内观察到抗原毒性作用。这表明体细胞和生殖细胞中的效应以一对一的比例发生。这些结果对人类的风险评估和分离食品成分的调节具有影响。 (C) 1998 Elsevier Science B.V. 保留所有权利。
The flavonoids, silymarin, myricetin, quercitin, kaempferol, rutin and kaempferol-3-rutinoside have been examined in combination with the food mutagens, 3-amino-1-methyl-5H-pyrido (4,3-b)indole (Trp-P-2) and 2-amino-3-methylimidazo-(4,5-f) quinoline (IQ), in the Comet assay in human lymphocytes from donor A and human sperm from donor B. These compounds alone have been shown to produce positive responses in the Comet assay, as have the food mutagens. However, in combination with the food mutagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in lymphocytes and sperm. The assays were performed in the absence of metabolic activation, since when quercetin and kaempferol were examined in blood with metabolic activation, there was little or no difference in response to that obtained in its absence. In the blood, there was an exacerbation or synergy of response at the lowest doses of the flavonoids. In the sperm, with silymarin, myricetin and quercitin, antigenotoxic effects only were observed, but with kaempferol, in general, there were no protective effects. The food mutagen, 2-amino-1-methyl-6-phenylimadazo (4,5-b)pyridine (PhIP), was also examined in addition to Trp-P-2 and IQ in combination with silymarin and myricetin in donors A and C in human lymphocytes only. Similar exacerbation of effects were found at low doses of these flavonoids with antigenotoxic effects at high doses. This was confirmed in the Ames test. There were slightly different profiles in lymphocytes and sperm, but antigenotoxic effects were observed over a similar dose range. This would suggest that effects occur in somatic and germ cells on a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents. (C) 1998 Elsevier Science B.V. All rights reserved.