Abstract
Abstract Background & Objectives: Azoxymethane (AOM) is a carcinogen that induces DNA lesions mainly repaired by the base excision repair (BER) pathway. Apurinic/apyrimidinic endonuclease 1 (APE1) is a central component of BER. Mice with homozygous deletion of the Apex1 gene (which encodes APE1) cannot survive development but heterozygous animals (Apex1+/-) have a normal lifespan. Our aim was to study the role of APE1 in the repair of DNA lesions and changes in mitochondrial DNA (mtDNA) abundance induced by AOM in the liver. Methods: We isolated DNA from 6-month-old C57BL/6 WT and Apex1+/- mice that were treated with a single AOM dose (10 mg/kg) and sacrificed 24, 48 and 72 hours after treatment. To quantify nuclear DNA (nDNA) lesions, mtDNA lesions and changes in mtDNA abundance in liver tissue we applied a PCR based assay (QPCR). Results: Our data show that 24h after AOM treatment both WT and Apex1+/- mice exhibit significant levels of nDNA and mtDNA damage. The lesion number decreases 48 and 72h after treatment but remains statistically elevated as compared to their respective controls. A two tailed ANOVA analysis shows no significant differences in DNA lesions between genotypes. However, Apex1+/- mice show a statistically significant 13% decrease in mtDNA abundance 72 hours after treatment. Conclusions: These results indicate that the liver is a major target of AOM and that APE1 plays a role in preventing AOM-induced loss of mtDNA abundance. Acknowledgments: Supported by R25GM061838, 2G12RR003051 and U54CA096297. Citation Format: Carlos A. Torres-Ramos, Adlin Rodriguez-Munoz, Joan Ballista-Hernandez, Ceidy Torres-Ortiz, Sylvette Ayala-Pena. Repair of azoxymethane-induced nuclear and mitochondrial DNA lesions in mouse liver [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5041.
Published Version
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