Anderson D, Dobrzyńska M M, Başaran N, Başaran A, Yu T W
BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK.
Mutat Res. 1998 Jun 18;402(1-2):269-77. doi: 10.1016/s0027-5107(97)00306-0.
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.
已将黄酮类化合物水飞蓟素、杨梅素、槲皮素、山奈酚、芦丁和山奈酚 -3-芸香糖苷，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（IQ）联合，在来自供体A的人淋巴细胞和来自供体B的人精子的彗星试验中进行检测。这些化合物单独使用时，在彗星试验中已显示会产生阳性反应，食品诱变剂也是如此。然而，与食品诱变剂联合使用时，黄酮类化合物产生了抗诱变作用，因为在淋巴细胞和精子的彗星试验中DNA损伤减少了。试验是在没有代谢活化的情况下进行的，因为当在有代谢活化的血液中检测槲皮素和山奈酚时，与在没有代谢活化时获得的反应几乎没有差异。在血液中，黄酮类化合物最低剂量时反应会加剧或产生协同作用。在精子中，仅观察到水飞蓟素、杨梅素和槲皮素具有抗诱变作用，但一般而言，山奈酚没有保护作用。除了Trp-P-2和IQ外，还在供体A和C的人淋巴细胞中，将食品诱变剂2-氨基-1-甲基-6-苯基咪唑(4,5 -b)吡啶（PhIP）与水飞蓟素和杨梅素联合进行了检测。在这些黄酮类化合物低剂量时发现了类似的效应加剧情况，高剂量时有抗诱变作用。这在艾姆斯试验中得到了证实。淋巴细胞和精子中的情况略有不同，但在相似的剂量范围内都观察到了抗诱变作用。这表明在体细胞和生殖细胞中效应是以一对一的比例发生的。这些结果在风险评估和分离食品成分的调节方面对人类具有重要意义。
