Ruf Afruj Ali, Jerwood David, Webb John, Anderson Diana
Department of Haematology, Airedale General Hospital, Steeton, United Kingdom.
Teratog Carcinog Mutagen. 2003;Suppl 2:83-91. doi: 10.1002/tcm.10078.
Thalassaemia is a heterogeneous group of inherited anaemias, characterised by a reduction or total absence of one or more of the globin chains of haemoglobin. Individuals with thalassaemia major require regular blood transfusions in order to maintain their haemoglobin concentration at an appropriate level. An essential treatment in parallel with transfusions is iron chelation therapy to remove excess iron deposited in tissues from the transfused blood. The high iron levels in these patients 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. In a previous study, it has been shown that peripheral blood lymphocytes isolated from a sickle/beta thal double heterozygote-sickle phenotype thalassaemia patient, who was not undergoing chelation therapy, showed increased sensitivity to the effects of oxygen radicals and iron salts by comparison with lymphocytes from normal controls. Furthermore, in a later study, this patient also 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. The present study, therefore, investigated whether the above observation could be duplicated using different food mutagens in different thalassaemia genotypes. The effect of 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, who were not undergoing chelation therapy were investigated using the Comet assay. All three thalassaemia genotypes showed increased sensitivity to both IQ and PhIP in comparison to the control, although with PhIP at the highest two concentrations (50 and 75 microM) the differences monitored with the alpha-thalassaemia trait were found not to be statistically significant (P > 0.05).
地中海贫血是一组遗传性贫血的异质性疾病，其特征是血红蛋白的一条或多条珠蛋白链减少或完全缺失。重型地中海贫血患者需要定期输血，以便将血红蛋白浓度维持在适当水平。与输血并行的一项重要治疗是铁螯合疗法，以清除输血后沉积在组织中的过量铁。这些患者体内的高铁水平使得游离氧自由基可以通过例如芬顿型化学反应产生，并产生超氧自由基和羟基自由基。已知氧自由基能力增加与癌症和衰老有关。在先前的一项研究中，已表明从未接受螯合治疗的镰状/β地中海贫血双杂合子-镰状表型地中海贫血患者分离出的外周血淋巴细胞，与正常对照的淋巴细胞相比，对氧自由基和铁盐的作用表现出更高的敏感性。此外，在后来的一项研究中，与对照组相比，该患者对饮食中的食物诱变剂3-氨基-1-甲基-5H-吡啶并(4,3-b)吲哚（Trp-P-2）也表现出更高的敏感性。因此，本研究调查了上述观察结果是否可以在不同的地中海贫血基因型中使用不同的食物诱变剂进行重复验证。使用彗星试验研究了食物诱变剂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）对三名未接受螯合治疗的不同地中海贫血患者淋巴细胞的影响，这三名患者分别是重型β地中海贫血、β地中海贫血/Hb E和具有3.7 kb缺失的α地中海贫血特征患者。与对照组相比，所有三种地中海贫血基因型对IQ和PhIP均表现出更高的敏感性，尽管对于PhIP在最高的两个浓度（50和75 microM）时，发现α地中海贫血特征患者监测到的差异无统计学意义（P>0.05）。
