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Chemoprevention of spontaneous tumorigenesis in p53-knockout mice
S D Hursting1, S N Perkins, D C Haines
1Laboratory of Nutritional and Molecular Regulation, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Abstract:
Spontaneous tumorigenesis was evaluated in male p53-knockout (p53-/-) mice treated with dehydroepiandrosterone (DHEA), quercetin, d-limonene, 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 lymphomas) 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 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.
Insights
Dehydroepiandrosterone (DHEA) delayed spontaneous tumor development and mortality in p53-knockout mice. Other tested cancer-chemopreventive agents did not affect tumor progression in this model.
Area of Science:
- Oncology
- Cancer Research
- Molecular Biology
Background:
- The p53 tumor suppressor gene is crucial for preventing cancer.
- Loss of p53 function increases susceptibility to spontaneous tumorigenesis.
- Cancer-chemopreventive agents are being investigated to mitigate cancer risk.
Purpose of the Study:
- To evaluate the efficacy of dehydroepiandrosterone (DHEA), quercetin, d-limonene, and all-trans retinoic acid in modulating spontaneous tumor development.
- To determine if p53-knockout (p53-/-) mice are a suitable model for testing cancer-chemopreventive strategies.
Main Methods:
- Spontaneous tumorigenesis was assessed in male p53-/- mice.
- Mice were treated with DHEA, quercetin, d-limonene, or all-trans retinoic acid.
- Tumor development and mortality rates were compared to untreated control groups.
Main Results:
- DHEA treatment significantly delayed the onset of spontaneous tumors, particularly lymphomas, and reduced subsequent mortality in p53-/- mice (P < 0.01).
- Quercetin, d-limonene, and all-trans retinoic acid did not show any significant effect on spontaneous tumor development in this model.
- These findings highlight DHEA's potential role in delaying cancer progression.
Conclusions:
- Dehydroepiandrosterone (DHEA) demonstrates a chemopreventive effect by delaying tumorigenesis in p53-/- mice.
- The p53-/- mouse model is validated as a useful platform for evaluating cancer-chemopreventive agents targeting loss of p53 function.
- Further research into DHEA and similar compounds may offer strategies to counteract the heightened cancer risk associated with p53 deficiency.