Anderson D, Dhawan A, Yardley-Jones A, Ioannides C, Webb J
TNO-BIBRA International Ltd., Woodmansterene Road, Carshalton SM54DS, Surrey, United Kingdom.
Teratog Carcinog Mutagen. 2001;21(2):165-74.
Thalassemia remains a significant health problem in Europe, the Middle East, and Asia. In such patients, generally high iron levels make free oxygen radicals accessible, for example, through Fenton-type chemistry, and generate superoxide and hydroxyl radicals. Increased oxygen radical capacity is known to be associated with cancer and ageing. It was shown in previous studies that peripheral blood lymphocytes from a sickle/beta thal double heterozygote-sickle phenotype, thalassemia patient, not yet on chelation therapy, were more sensitive to the effects of oxygen radicals and iron salts than lymphocytes from normal controls. Iron overload in thalassemia patients can result from dietary absorption. It was considered that with other dietary agents, such as food mutagens and flavonoids, the thalassemia patient might also show increased sensitivity to the effects of these agents. The present study, therefore, compared the effects of the food mutagen/carcinogen, 3-amino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2), in fresh or frozen normal human peripheral lymphocytes with frozen lymphocytes from the same thalassemia patient. The lymphocytes from the thalassemia patient showed an approximately two-fold increase in sensitivity. When a combination of Tryp-P-2, with either quercitin or kaempferol, was compared in frozen lymphocytes and lymphocytes from the thalassemia patient, a two-fold increase in sensitivity was also maintained. Responses to Trp-P-2 were reduced to untreated control levels at the highest doses of quercitin and kaempferol, and were highly significantly different by comparison with Trp-P-2 alone (P<0.001). The flavonoids acted in an antigenotoxic/antioxidant manner. Sensitivity was slightly increased with kaempferol by comparison with quercitin. At low concentrations of the flavonoids there was some evidence of an exacerbation of response, perhaps due to a switch to pro-oxidant status. This exacerbation of response at low doses of flavonoids has been seen in earlier studies with normal lymphocytes. Teratogenesis Carcinog. Mutagen. 21:165-174, 2001.
地中海贫血在欧洲、中东和亚洲仍然是一个严重的健康问题。在这类患者中，通常较高的铁水平使得游离氧自由基能够产生，例如通过芬顿型化学反应产生超氧化物和羟基自由基。已知氧自由基能力的增加与癌症和衰老有关。先前的研究表明，来自镰状/β地中海贫血双重杂合子-镰状表型、尚未接受螯合治疗的地中海贫血患者的外周血淋巴细胞比正常对照的淋巴细胞对氧自由基和铁盐的作用更敏感。地中海贫血患者的铁过载可能源于饮食吸收。人们认为，与其他饮食因素，如食物诱变剂和类黄酮一起，地中海贫血患者可能对这些因素的作用也表现出更高的敏感性。因此，本研究比较了食物诱变剂/致癌物3-氨基-1-甲基-5H-吡啶并(4,3-b)吲哚(Trp-P-2)对新鲜或冷冻的正常人外周淋巴细胞以及来自同一名地中海贫血患者的冷冻淋巴细胞的影响。地中海贫血患者的淋巴细胞敏感性增加了约两倍。当将Trp-P-2与槲皮素或山奈酚联合使用，并在冷冻淋巴细胞和地中海贫血患者的淋巴细胞中进行比较时，敏感性也保持增加了两倍。在槲皮素和山奈酚的最高剂量下，对Trp-P-2的反应降低到未处理对照水平，与单独使用Trp-P-2相比有极显著差异(P<0.001)。类黄酮以抗基因毒性/抗氧化的方式起作用。与槲皮素相比，山奈酚使敏感性略有增加。在类黄酮低浓度时，有一些证据表明反应加剧，这可能是由于转变为促氧化状态所致。在早期对正常淋巴细胞的研究中也观察到了低剂量类黄酮时这种反应加剧的情况。《致畸学、致癌学、诱变学》2001年第21卷，第165 - 174页
