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 r adicals accessible, for example, through Fenton-type chemistry, and generat e superoxide and hydroxyl radicals. Increased oxygen radical capacity is kn own to be associated with cancer and ageing. It was shown in previous studi es that peripheral blood lymphocytes from a sickle/beta thal double heteroz ygote-sickle phenotype, thalassemia patient, not yet on chelation therapy, were more sensitive to the effects of oxygen radicals and iron salts than l ymphocytes from normal controls. Iron overload in thalassemia patients can result from dietary absorption. It was considered that with other dietary a gents, such as food mutagens and flavonoids, the thaIassemia 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-a mino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2), in fresh or frozen normal h uman peripheral lymphocytes with frozen lymphocytes from the same thalassem ia patient. The lymphocytes from the thalassemia patient showed an approxim ately two-fold increase in sensitivity. When a combination of Tryp-P-2, wit h either quercitin or kaempferol, was compared in frozen lymphocytes and ly mphocytes 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 s i,significantly different by comparison with Trp-P-2 alone (P<0.001). The f lavonoids acted in an antigenotoxic/antioxidant manner. Sensitivity was sli ghtly increased with kaempferol by comparison with quercitin. At low concen trations of the flavonoids there was some evidence of an exacerbation of re sponse, 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. (C) 2001 Wiley-Liss, Inc.