Treatment of Wistar rats with a renal carcinogen, ferric nitrilotriacetate, causes DNA-protein cross-linking between thymine and tyrosine in their renal chromatin.
Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular damage associated with lipid peroxidation and oxidative DNA base modifications that finally leads to a high incidence of renal adenocarcinoma in rodents. In the present study, we report on the in vivo formation of DNA-protein cross-links (DPCs) involving thymine and tyrosine in the renal chromatin of Wistar rats treated with single or repeated i.p. administration of Fe-NTA. Analyses of chromatin samples by gas chromatography/mass spectrometry revealed a significant increase in the amount of 3-[(1,3-dihydro-2,4-dioxopyrimidin-5-yl)-methyl]-L-tyrosine (Thy-Tyr cross-link) 24 and 48 hr after the administration of Fe-NTA. At 19th day of Fe-NTA treatment, the amount of Thy-Tyr cross-link decreased to the control level, indicating the presence of cellular repair activity. Thy-Tyr cross-link may play a role in the genetic alteration of this renal carcinogenesis model, since mitoses for regeneration of renal proximal tubules were closely associated with the increase in DPCs.
Toyokuni
S
S
Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
Mori
T
T
Hiai
H
H
Dizdaroglu
M
M
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002843:Chromatin / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism / Q000633:toxicity; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013941:Thymine / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D002273:Carcinogens; D002843:Chromatin; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D005290:Ferric Compounds; D009363:Neoplasm Proteins; D014443:Tyrosine; D009571:Nitrilotriacetic Acid; D013941:Thymine; C020326:ferric nitrilotriacetate