PARENT SESSION

Mutagenesis & Carcinogenesis

(MS030) Characterization of -radiation induced tumorigenesis with a humanized-p53 mouse model.

Dudgeon, Crissy ¹, Li, Henghong^*,2, Bulavin, Dmitry ³, Fornace, Albert ¹, ¹ Dept. of Genetics and Complex Diseases, Boston, MA, US² Center for Cancer Research, Bethesda, MD, US³

ABSTRACT- Human and mouse p53 proteins share 77% similarity but there are important differences in some regulatory regions. We have generated a new mouse strain, carrying a human p53 transgene in the Trp53-/- background (designated TP53;Trp53-/-). Expression of human p53 in the Trp53-/- background fails to restore the -ray-induced apoptotic response, and does not prevent accelerated tumor development after -radiation. However these mice do not show early onset of spontaneous tumors as typically seen for Trp53-/- mice. Quantitative single-probe hybridization and RT-PCR were used to determine the relative mRNA levels for selected p53 target genes. The preliminary results indicate that human p53 is deficient in transactivating target genes in this model. To extend this to global analysis of stress gene expression, we are carrying out a functional genomics approach to analyze gene induction and repression in response to -radiation. By comparing the expression profiles with Trp53+/+ mice, our objective is to be able to filter out response genes critical for -radiation induced tumorigenesis but dispensable for the onset of spontaneous tumorigenesis.

Key words: ã-radiation induced tumorigenesis, functional genomics, mouse model, Trp53-/- mice