Accumulation of lipid peroxidation-derived DNA lesions in iron-overloaded thalassemic mouse livers: Comparison with levels in the lymphocytes of thalassemia patients

• Main Authors: Meerang M., Nair J., Sirankapracha P., Thephinlap C., Srichairatanakool S., Arab K., Kalpravidh R., Vadolas J., Fucharoen S., Bartsch H.
• Format: Article
• Language: English
• Published: 2014
• Online Access: http://www.scopus.com/inward/record.url?eid=2-s2.0-67650065532&partnerID=40&md5=959f4dd549790c51844440796e3e7dfd; http://cmuir.cmu.ac.th/handle/6653943832/2812
• Institution: Chiang Mai University

In thalassemia patients, iron overload can stimulate lipid peroxidation (LPO), thereby generating miscoding DNA adducts. Adducted DNA was measured in the lymphocytes of β-Thal/Hb E patients and healthy controls and in the organs of thalassemic mice. εdA, εdC and M1dG residues were quantified by 32P-postlabeling-TLC/HPLC. M1dG levels in lymphocyte DNA from patients were 4 times as high as in controls, while the increase in εdA and εdC was not significant. Adducted DNA accumulated in the liver of thalassemic mice having >2.7 mg Fe/g tissue dry weight; DNA adducts and iron were highly correlated. edA was not specifically generated in certain mouse liver cell types as revealed by immunohistochemical staining. We found elevated LPO-induced DNA damage in the liver of thalassemic mouse and in lymphocytes, implicating that massive DNA damage occurs in the liver of thalassemia patients. We conclude that promutagenic LPO-derived DNA lesions are involved in the onset of hepatocellular carcinoma in these patients. © 2009 UICC.