We have located links that may give you full text access.
Journal Article
Research Support, U.S. Gov't, P.H.S.
Review
Cancer predisposition in mutant mice defective in multiple genetic pathways: uncovering important genetic interactions.
Mutation Research 2001 June 3
Mouse models that mimic the human skin cancer-prone disease xeroderma pigmentosum (XP) provide an useful experimental system with which to study the relationship between the DNA repair process of nucleotide excision repair (NER) and ultraviolet- (UV) induced skin carcinogenesis. We have generated Xpc mutant mice and documented their deficiency in the process of NER of UV-induced DNA damage. Xpc mutant mice are highly predisposed to UV-B radiation-induced skin cancer, both in the homozygous and the heterozygous state. The combination of Xpc and Trp53 mutations enhances this predisposition and alters the tumor spectrum observed in single mutant mice. These results suggest a synergism between NER and the function of Trp53 in suppression of cancer. We have examined the mutational spectrum in the Trp53 gene from skin cancers in Trp53+/+ and Trp53+/- mice of all three Xpc genotypes and have found evidence for signature mutations associated with defective NER. In addition, we have demonstrated that Xpc mutant mice are highly predisposed to the induction of lung and liver cancers by treatment with 2-acetylaminofluorene (2-AAF) and N-OH-2-AAF. By combining the Xpc mutation with other mutations in genes involved in repair of DNA damage we have identified additional genetic interactions important in carcinogenesis. The mouse Apex gene is a critical component of the base excision repair (BER) pathway as well as the redox regulation of transcription factors important in growth control and the cellular response to DNA damage. By combining mutations in Xpc, Trp53 and Apex we have obtained genetic evidence for a functional interaction between Apex and Trp53 which probably involves the activation of the Trp53 protein by Apex. Mutations in the mismatch repair (MMR) gene Msh2 also influence the carcinogenesis observed in Xpc Trp53 mutant mice. Our results demonstrate that multiple repair pathways operate in prevention of tumor formation.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app