Author(s): Toyokuni S, Mori T, Hiai H, Dizdaroglu M
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Abstract 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.
This article was published in Int J Cancer
and referenced in Journal of Gastrointestinal & Digestive System