Increased urinary 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine excretion in thalassemia patients: Markers for lipid peroxidation-induced DNA damage

• Main Authors: Mayura Meerang, Jagadeesan Nair, Pornpan Sirankapracha, Chonthida Thephinlap, Somdet Srichairatanakool, Suthat Fucharoen, Helmut Bartsch
• Other Authors: German Cancer Research Center
• Format: Article
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Medicine; Pharmacology, Toxicology and Pharmaceutics
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/18919
• Institution: Mahidol University

Thalassemic diseases including homozygous β-thalassemia and β-thalassemia/Hb E (β-Thal/Hb E) are prevalent in Southeast Asia. Iron overload is a common complication in β-thalassemia patients which induces intracellular oxidative stress and lipid peroxidation (LPO). LPO end products generate miscoding etheno adducts in DNA which after their repair are excreted in urine. We investigated whether urinary levels of 1,N6-ethenodeoxyadenosine (εdA) and 3,N4-ethenodeoxycytidine (εdC) can serve as putative cancer risk markers in β-Thal/Hb E patients. εdA and εdC levels were assayed in collected urine samples by immunoprecipitation-HPLC-fluorescence and32P-postlabeling TLC, respectively. Mean εdA (fmol/μmol creatinine) levels in urine of β-Thal/Hb E patients ranged from 4.8 to 120.4 (33.8 ± 3.9; n = 37) and were 8.7 times higher compared to asymptomatic controls (1.4-13.8; 3.9 ± 0.8; n = 20). The respective εdC levels ranged from 0.15 to 32.5 (5.2 ± 1.3; n = 37) and were increased some 13 times over controls (0.04-1.2; 0.4 ± 0.7; n = 20). εdC levels were correlated positively with NTBI (r = 0.517; P = 0.002), whereas εdA showed only a trend (r = 0.257; P = 0.124). We conclude that the strongly increased urinary excretion of etheno adducts indicates elevated LPO-induced DNA damage in internal organs such as the liver. These highly promutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma. © 2008 Elsevier Inc. All rights reserved.