Chemopreventionof SpontaneousTumorigenesisin p53-KnockoutMice1

Spontaneous tumorigenesis was evaluated in male p53-knockout (p53~'~) mice treated with dehydroepiandrosterone (DHEA), quercetin, J-limonene, or iM-trans retinole acid to determine whether tumor devel opment in these mice can be modulated by cancer-chemopreventive agents. DHEA-treated mice experienced a delay in tumorigenesis (partic ularly lymphomas) and subsequent mortality (I' < 0.01) relative to un treated control mice. Quercetin, (/-limonaie, and ;\\\-trun\ retinoic acid each had no effect on spontaneous tumor development in p53~'~ mice. These data demonstrate that tumor development in p53~'~ mice can be delayed by DHEA and suggest that p53~' mice provide a useful model for evaluating strategies to offset the increased risk of tumorigenesis resulting from loss of p53 tumor suppressor function.