Radiation induced tumor development and genomic instability

Abstract

Radiation carcinogenesis is thought to be the results of a series of somatic mutations. Translesion synthesis is the major source of DNA damage-induced point mutations. Y family DNA polymerases which operate Translesion DNA synthesis TLS can bypass a various damage lesions with low fidelity. Rev1 has a regulatory role in TLS. However defect of Rev1 is sensitive to radiation, expression of Rev1 mutant, which is deleted its catalytic function in translesion synthesis, can recover this sensitivity. These demonstrate Rev1 has catalytic and non-catalytic function in radioresponse. However, little is known whether Rev1 protein has the precise role in radiation-induced tumorigenesis in vivo. We generated Rev1 transgenic mice that continuously express a Rev1transgene in various tissues. Both Rev1 Tg and wild-type (Wt) mice were subjected to gamma-irradiation of 1.6Gy four times at a weekly internal, starting at the age of 4 weeks. Our data demonstrates that overexpression of Rev1 may be associated with raditation-induced tumorigenesis.