title: Sensitivity of different thalassaemia genotypes to food mutagens in the Comet assay.
abstract: 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).
authors.affiliation: Department of Haematology, Airedale General Hospital, Steeton, United Kingdom.
authors.forename: Afruj Ali
authors.initials: AA
authors.lastname: Ruf
authors.forename: David
authors.initials: D
authors.lastname: Jerwood
authors.forename: John
authors.initials: J
authors.lastname: Webb
authors.forename: Diana
authors.initials: D
authors.lastname: Anderson
mesh_terms: D002675:Child, Preschool; D020552:Comet Assay; D004247:DNA / Q000187:drug effects*; D004361:Drug Tolerance; D005260:Female; D005502:Food; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D007501:Iron / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017085:alpha-Thalassemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; D017382:Reactive Oxygen Species; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D007501:Iron