Increased urinary 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine excretion in thalassemia patients: markers for lipid peroxidation-induced DNA damage.
Thalassemic diseases including homozygous beta-thalassemia and beta-thalassemia/Hb E (beta-Thal/Hb E) are prevalent in Southeast Asia. Iron overload is a common complication in beta-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 (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) can serve as putative cancer risk markers in beta-Thal/Hb E patients. epsilondA and epsilondC levels were assayed in collected urine samples by immunoprecipitation-HPLC-fluorescence and 32P-postlabeling TLC, respectively. Mean epsilondA (fmol/micromol creatinine) levels in urine of beta-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 epsilondC 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). epsilondC levels were correlated positively with NTBI (r=0.517; P=0.002), whereas epsilondA 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.
Meerang
Mayura
M
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany. m.meerang@gmail.com
Nair
Jagadeesan
J
Sirankapracha
Pornpan
P
Thephinlap
Chonthida
C
Srichairatanakool
Somdet
S
Fucharoen
Suthat
S
Bartsch
Helmut
H
D000328:Adult; D014408:Biomarkers, Tumor / Q000652:urine; D004249:DNA Damage; D003839:Deoxyadenosines / Q000652:urine*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D013789:Thalassemia / Q000652:urine*
D014408:Biomarkers, Tumor; D003839:Deoxyadenosines; D003841:Deoxycytidine; C032221:1,N(6)-ethenodeoxyadenosine; C032222:3,N(4)-ethenodeoxycytidine