Ruf Afruj Ali, Webb John, Anderson Diana
Department of Haematology, Airedale General Hospital, Steeton, United Kingdom.
Teratog Carcinog Mutagen. 2003;Suppl 2:93-102. doi: 10.1002/tcm.10083.
Thalassaemia is an inherited group of disorders caused by a reduction or total absence of one or more of the globin chains of the haemoglobin molecule. It has been shown that lymphocytes isolated from a sickle/beta thal double heterozygote-sickle phenotype patient showed increased sensitivity to the dietary food mutagen 3-amino-1-methyl-5H-pyridol(4,3-b)indole (Trp-P-2) when compared to the control. Furthermore, when a combination of Trp-P-2 with either quercitin or kaempferol was compared, the responses to Trp-P-2 were reduced to untreated control levels at the highest doses of quercitin and kaempferol. It has now been shown that using the food mutagens 2-amino-2-methylimidazolo(4,5-f)quinolone (IQ) and 2-amino-1-methyl-6-phenylimidazol(4,5-b)pyridine (PhIP) on lymphocytes of three different thalassaemia patients, a beta-thalassaemia major, a beta-thalassaemia/Hb E, and an alpha-thalassaemia trait with a 3.7-kb deletion, similar increased sensitivity could also be demonstrated. The present study investigated whether the modulatory effects of the flavonoids could be demonstrated in lymphocytes isolated from a beta-thalassaemia major and a beta-thalassaemia/Hb E patient. Lymphocytes from both a beta-thalassaemia major and beta-thalassaemia/Hb E patient showed increased sensitivity to PhIP when compared to the normal control. When a combination of PhIP and either quercitin or kaempferol was used, a reduction in the responses was seen, and at the highest doses of quercitin and kaempferol the responses were reduced to near untreated control levels and were significantly different when compared to PhIP alone (P < 0.05). It was concluded that lymphocytes from different thalassaemia genotypes showed increased sensitivity to different dietary food mutagens compared to normal lymphocytes and that flavonoids such as quercitin and kaempferol modulated the effects of these food mutagens in an antigenotoxic/antioxidant manner.
地中海贫血是一组遗传性疾病，由血红蛋白分子的一条或多条珠蛋白链减少或完全缺失引起。研究表明，与对照组相比，从一名镰状细胞/β地中海贫血双重杂合子-镰状细胞表型患者分离出的淋巴细胞对膳食诱变剂3-氨基-1-甲基-5H-吡啶并(4,3-b)吲哚（Trp-P-2）表现出更高的敏感性。此外，当比较Trp-P-2与槲皮素或山奈酚的组合时，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的对照水平。现已表明，使用食物诱变剂2-氨基-2-甲基咪唑并(4,5-f)喹啉（IQ）和2-氨基-1-甲基-6-苯基咪唑并(4,5-b)吡啶（PhIP）作用于三名不同地中海贫血患者（一名重型β地中海贫血患者、一名β地中海贫血/Hb E患者和一名具有3.7-kb缺失的α地中海贫血特征患者）的淋巴细胞时，也能证明类似的敏感性增加。本研究调查了在从一名重型β地中海贫血患者和一名β地中海贫血/Hb E患者分离出的淋巴细胞中是否能证明黄酮类化合物的调节作用。与正常对照相比，重型β地中海贫血患者和β地中海贫血/Hb E患者的淋巴细胞对PhIP均表现出更高的敏感性。当使用PhIP与槲皮素或山奈酚的组合时，反应出现降低，在槲皮素和山奈酚的最高剂量下，反应降低到接近未处理的对照水平，与单独使用PhIP相比有显著差异（P < 0.05）。得出的结论是，与正常淋巴细胞相比，不同地中海贫血基因型的淋巴细胞对不同的膳食诱变剂表现出更高的敏感性，并且槲皮素和山奈酚等黄酮类化合物以抗诱变/抗氧化的方式调节这些食物诱变剂的作用。
