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

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-...

Full description

Saved in:
Bibliographic Details
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:
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=67650065532&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/59352
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Chiang Mai University
Description
Summary: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.