title: Modulation by flavonoids of the effects of a food mutagen in different thalassaemia genotypes in the Comet assay.
abstract: 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.
authors.affiliation: Department of Haematology, Airedale General Hospital, Steeton, United Kingdom.
authors.forename: Afruj Ali
authors.initials: AA
authors.lastname: Ruf
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; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005502:Food; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects; D044949:Kaempferols / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009153:Mutagens / Q000633:toxicity*; D011794:Quercetin / Q000494:pharmacology; D011804:Quinolines / Q000633:toxicity*; D017085:alpha-Thalassemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D005419:Flavonoids; D007093:Imidazoles; D044949:Kaempferols; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C006552:kaempferol; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D011794:Quercetin