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

• Main Authors: Mayura Meerang, Jagadeesan Nair, Pornpan Sirankapracha, Chonthida Thephinlap, Somdet Srichairatanakool, Khelifa Arab, Ruchaneekorn Kalpravidh, Jim Vadolas, Suthat Fucharoen, Helmut Bartsch
• Format: Journal
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Medicine
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=67650065532&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/48858
• 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.