Determination of genetic abnormalities with genotoxicity testing in peripheral lymphocytes of Beta thalassemia major patients

Thalassemia major, is a hematological disease that is caused by absence or lower than normal production of globulin chains of hemoglobins. Most of the patients need erythrocyte transfusion to survive and this leads to serious complications. To prevent these complications iron chelating agents like ?deferoxamine (DFO), deferiprone (DFP), deferasirox? are used. Although these agents remove accumulated iron from tissues, recent studies showed that they may also have genotoxic effects.The aim of this study is to determine possible genotoxic effects of Deferoxamine, Deferiprone and Deferasirox which have to be used by patients who have thalassemia major. The relationship between iron load and the genetic abnormalities have also been studied. For this purpose, structural chromosomal abnormalities and primary DNA damage were determined by using Chromosomal Abnormalities (CA), Sister Chromatid Exchange (SCE), Micronucleus (MN) and Comet tests in 51 patients with thalassemia and 30 healthy individuals.In this study it was found that chromosomal abnormality frequency is significantly higher in the patients between ages 0-20 compared to control group, on the other hand no significant difference is present between patients and controls over 20 years of age. Chromosomal abnormality frequency is also higher in patients using DFO and Deferasiroks. On the other hand, in the group receiving combined chelator therapy with DFO+DFP, despite older age and higher ferritin values chromosomal abnormality frequency is not different from the control group. In the TM group mitotic index is found to have inverse relationship with age and it decreases more with increasing age in the TM group than in the control group. The patient group receiving DFO has the lowest mitotic index.It was observed that SCE and MN frequencies increase after 10 years of age in the TM patient group. The groups receiving DFO alone and combined DFO+DFP treatment have the highest SCE number. MN frequency is found high in the cases taking Deferasiroks and combined DFO+DFP treatment. MN frequency is low in patients taking DFO. Replication index (RI) and nuclear division index (NBI) values are lower compared to the control group but not significantly. Primary DNA damage was evaluated according to age and found that it increases in the group 0-10 years and above 20 years of age but there is no significant change in the 10-20 years group. When evaluated according to drug intake, it was detected that primary DNA damage is siginificantly higher than the control group. It was searched whether the drug subtype has an effect on this increment, and found that there was an increase for all drugs but in the combined DFO+DFP group it was a bit higher but not significant.In conclusion; in patients with TM, increasing number of blood transfusions lead to increased iron accumulation in the organs with increasing age. This leads to genotoxic damage due to oxidative stress. Genotoxic effects of iron chelating agents were compared ex vivo. Future in vitro studies may support these conclusions. Conclusion of this study will be useful for clinical guidance and in determining iron chelating drug therapy protocol