Effect of antioxidant flavonoids and a food mutagen on lymphocytes of a thalassemia patient without chelation therapy in the Comet assay.
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.
TNO-BIBRA International Ltd., Woodmansterene Road, Carshalton SM54DS, Surrey, United Kingdom. danderson@bibra.co.uk
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Anderson
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Dhawan
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Yardley-Jones
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Ioannides
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Webb
D002243:Carbolines; D002273:Carcinogens; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000009:adverse effects*; D020552:Comet Assay / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000009:adverse effects*; D006801:Humans; D007501:Iron / Q000378:metabolism; D044949:Kaempferols; D008214:Lymphocytes / Q000187:drug effects*; D009153:Mutagens; D011794:Quercetin / Q000009:adverse effects / Q000031:analogs & derivatives; D012680:Sensitivity and Specificity; D013789:Thalassemia / Q000235:genetics* / Q000378:metabolism*
D002243:Carbolines; D002273:Carcinogens; D002614:Chelating Agents; D005419:Flavonoids; D044949:Kaempferols; D009153:Mutagens; C006552:kaempferol; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D011794:Quercetin; D007501:Iron