Project description:Intraperitoneal administration of ferric nitrilotriacetate initiates Fenton reaction in the renal proximal tubules in rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC) after repeated treatment. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of oxidative stress-induced RCCs and simultaneously developed malignant lymphomas in the mice. The results highlighted a substantial difference in the predisposition to chromosomal changes between animal species.
Project description:Intraperitoneal administration of ferric nitrilotriacetate initiates Fenton reaction in the renal proximal tubules in rodents. Its repeated administration ultimately leads to the development of renal cell carcinoma (RCC). We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of oxidative stress-induced RCCs in the mice of A/J strain.
Project description:Oxidative DNA damage has been associated with cognitive decline. The Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic oxidative DNA base lesion. Here, we have examined behavior and cognitive function in mice deficient of these glycosylases. We found that Ogg1-/-Mutyh-/- mice were more active and less anxious and that their learning ability was impaired. In contrast, Mutyh-/- mice showed moderately improved memory compared to WT. There was no change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutant mice belong to pathways known to be involved in anxiety and cognitive function. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh modulate cognitive function and behavior, and related hippocampal gene expression, suggesting a novel role for 8-oxoG in regulating adaptive behavior.
Project description:Intraperitoneal administration of ferric nitrilotriacetate (Fe-NTA) initiates Fenton reaction in the renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC) after repeated treatment. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletion.
Project description:Intraperitoneal administration of ferric nitrilotriacetate (Fe-NTA) initiates Fenton reaction in the renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC) after repeated treatment. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletion. Carcinogenesis protocol was performed using male F1 hybrid rats between Fischer344 and Brown-Norway strains. 13 primary tumors and 2 cell lines of Fe-NTA induced RCCs were profiled on Agilent 185K rat genome CGH microarrays. One RCC sample of a female Eker rat was also analyzed with the same Agilent 185K rat genome CGH microarray.
