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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thalassaemia is a group of genetic diseases where haemoglobin synthesis is impaired. This chronic anaemia leads to increased dietary iron absorption, which develops into iron overload pathology. Treatment through regular transfusions increases oxygen capacity but also provides iron through the red cells' haemoglobin. An essential treatment, in parallel with transfusions, is the use of chelating agents to remove the excess iron deposited in tissues. These deposits are found in the liver, spleen, heart, and pancreas and are associated with cardiac failure and diabetes. The deposits in these tissues of patients have been isolated as haemosiderin. Thalassaemia patients are particularly at risk of free radical induced damage. Thus, the present study has investigated, as a model system, human cells in vitro in the Comet assay in the presence of free radicals. This assay measures DNA damage, particularly DNA strand breakage. The effects of iron overload on cells oxidatively stressed with hydrogen peroxide (H(2)O(2)) have been determined as well as the effect of the chelating agent, deferoxamine. Iron overload was simulated with ferric (FeCl(3)) and ferrous chloride (FeCl(2)), ferrous sulphate (FeSO(4)) and haemosiderins. Both human lymphocytes from a male and a female donor and human adenocarcinoma colonic cells showed an increase in DNA damage in the Comet assay after treatment with H(2)O(2). Ferric chloride produced an increase in DNA damage in human colonic cells, but little or no damage in human lymphocytes. Ferrous chloride also produced weak DNA damage in human lymphocytes, but ferrous sulphate produced a dose-related response. Deferoxamine produced no DNA damage. When H(2)O(2) was combined with FeCl(3), FeCl(2), or FeSO(4), the DNA damage produced was as least as great as or slightly greater than with H(2)O(2) alone. When deferoxamine was combined with H(2)O(2) and FeSO(4) there was a consistent decrease in response. There was little or no decrease in response when deferoxamine was combined with H(2)O(2) and FeCl(3) or FeCl(2), but at high (100-300microm) doses there were changes in the appearance of cellular DNA from Comet tails to dense centres surrounded by a diffuse area. This was probably as a consequence of chelation processes. Haemosiderin produced no damage. The three fractions of haemosiderin examined were of three different densities and from a Thai patient where the oxyhydroxide phase is the ferrihydrite. The colour change was similar to that for FeCl(3), but the level of the ferric ion in the haemosiderin was possibly too low in the sample to produce a response. The next stage is to examine peripheral lymphocytes from thalassaemic patients, with and without chelation therapy, whose cells may be more sensitive to simulated iron overload and to lower levels of haemosiderin. Teratogenesis Carcinog. Mutagen. 20:11-26, 2000.
Teratog Carcinog Mutagen 2000
PMID:Effects of iron salts and haemosiderin from a thalassaemia patient on oxygen radical damage as measured in the comet assay. 1060 74

Impairment of haemoglobin synthesis occurs in the genetic diseases known as thalassaemia. The consequent chronic anaemia leads to increased dietary iron absorption which results in iron overload. Treatment through regular blood transfusions increases oxygen capacity, but also adds iron from haemoglobin. An essential treatment, in parallel with transfusions, is the use of chelating agents to remove the excess iron. Thalassaemia patients are particularly at risk of free radical damage. Human lymphocytes from normal individuals can be investigated in vitro as a model system in the presence of free radicals in the Comet assay. This assay measures DNA damage, particularly DNA strand breakage. We examined cells from an Australian thalassaemic patient (sickle/beta thal double heterozygote-sickle phenotype) who had not yet received chelation therapy to determine if the cells were more sensitive to simulated iron overload and to haemosiderins. Lymphocytes from the patient were received as frozen samples after 28 h on dry ice and then placed in liquid nitrogen. Normal lymphocytes frozen under the same conditions and normal nonfrozen lymphocytes were compared. The lymphocytes from a normal female did not respond in vitro to ferric chloride (FeCl(3)) or haemosiderin but did to ferrous chloride (FeCl(2)) and ferrous sulphate (FeSO(4)). Deferoxamine appeared to reduce the response to FeCl(2) and FeSO(4) but deferiprone did not. When the lymphocytes from the nonchelated patient were treated with FeSO(4) and hydrogen peroxide, deferoxamine and deferiprone both reduced the response. Over the same dose range of iron salt (FeSO(4)), the lymphocytes from the thalassaemic patient were more sensitive, with much higher background levels of damage and induced damage. When deferiprone and deferoxamine were compared over a nontoxic range, deferiprone appeared to produce a greater reduction of damage in lymphocytes of the thalassaemia patient. Ferritin iron appears to be more available than haemosiderin iron in reactions leading to DNA damage. Haemosiderin containing higher amounts of the goethite-like (alpha-FeOOH) iron oxide phase leads to lower levels of DNA damage.
Teratog Carcinog Mutagen 2000
PMID:Effect of iron salts, haemosiderins, and chelating agents on the lymphocytes of a thalassaemia patient without chelation therapy as measured in the comet assay. 1099 72

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.
Teratog Carcinog Mutagen 2001
PMID:Effect of antioxidant flavonoids and a food mutagen on lymphocytes of a thalassemia patient without chelation therapy in the Comet assay. 1122 93

Thalassaemia is a heterogeneous group of inherited anaemias, characterised by a reduction or total absence of one or more of the globin chains of haemoglobin. Individuals with thalassaemia major require regular blood transfusions in order to maintain their haemoglobin concentration at an appropriate level. An essential treatment in parallel with transfusions is iron chelation therapy to remove excess iron deposited in tissues from the transfused blood. The high iron levels in these patients 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. In a previous study, it has been shown that peripheral blood lymphocytes isolated from a sickle/beta thal double heterozygote-sickle phenotype thalassaemia patient, who was not undergoing chelation therapy, showed increased sensitivity to the effects of oxygen radicals and iron salts by comparison with lymphocytes from normal controls. Furthermore, in a later study, this patient also 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. The present study, therefore, investigated whether the above observation could be duplicated using different food mutagens in different thalassaemia genotypes. The effect of 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, who were not undergoing chelation therapy were investigated using the Comet assay. All three thalassaemia genotypes showed increased sensitivity to both IQ and PhIP in comparison to the control, although with PhIP at the highest two concentrations (50 and 75 microM) the differences monitored with the alpha-thalassaemia trait were found not to be statistically significant (P > 0.05).
Teratog Carcinog Mutagen 2003
PMID:Sensitivity of different thalassaemia genotypes to food mutagens in the Comet assay. 1469 82

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.
Teratog Carcinog Mutagen 2003
PMID:Modulation by flavonoids of the effects of a food mutagen in different thalassaemia genotypes in the Comet assay. 1469 83