Treatment of wistar rats with a renal carcinogen, ferric nitrilotriacetate, causes dna-protein cross-linking between thymine and tyrosine in their renal chromatin
✍ Scribed by Shinya Toyokuni; Toshiaki Mori; Hiroshi Hiai; Miral Dizdaroglu
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- French
- Weight
- 673 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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-[( I ,3-dihydro-2,4-dioxopyrimidin-5-yl)-methyl]-Ltyrosine (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.