CHEMOPREVENTION OF SPONTANEOUS TUMORIGENESIS IN P53-KNOCKOUT MICE

Spontaneous tumorigenesis was evaluated in male p53-knockout (p53(-/-) ) mice treated with dehydroepiandrosterone (DHEA), quercetin, d-limone ne, or all-trans retinoic acid to determine whether tumor development in these mice can be modulated by cancer-chemopreventive agents, DHEA- treated mice experienced a delay in tumorigenesis (particularly lympho mas) and subsequent mortality (P < 0.01) relative to untreated control mice. Quercetin, d-limonene, and all-trans retinoic acid each had no effect on spontaneous tumor development in p53(-/-) mice. These data d emonstrate that tumor development in p53(-/-) mice can be delayed by D HEA and suggest that p53(-/-) mice provide a useful model for evaluati ng strategies to offset the increased risk of tumorigenesis resulting from loss of p53 tumor suppressor function.