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.