Accelerated development of polyoma tumors and embryonic lethality: Different effects of p53 loss on related mouse backgrounds

Molecular evidence linking polyoma virus to p53 inactivation is thus far la cking, setting this highly oncogenic Virus apart from other DNA tumor virus es. As a biological test for interaction, we studied the effects of p53 los s on development of virus-induced tumors. The absence of p53 led to more ra pid tumor development on two different mouse backgrounds, indicating synerg ism between p53 loss and oncogenic pathways controlled directly by the viru s, No effects of p53 on tumor type or frequency were noted, Polyoma tumor-d erived cells in culture retained p53, and most of these showed induction of p21(CIP1/WAF1) in response to DNA damage. These results indicate that p53 functions are not directly and fully impaired by the virus in the intact ho st, On one mouse background, it was discovered that loss of p53 resulted in complete embryonic lethality prior to 11 days of gestation, This lethality could be rescued by inclusion of gene(s) from a 129/SvJ background.