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Induction of squamous cell carcinoma in p53-deficient mice after ultraviolet irradiation
1Department of Medicine, Vancouver Hospital and Health Sciences Center, The University of British Columbia, Canada.
Abstract:
Mutations of the p53 gene have been implicated as an important factor in the pathogenesis of ultraviolet light induced skin cancers. To examine the role of p53 in skin carcinogenesis, we observed the development of skin cancers in homozygous p53-deficient (-/-) mice and wild-type p53 (+/+) mice, after chronic ultraviolet B (290-320 nm) exposure. At a dose of 2 J per m2 per s of ultraviolet B for 30 min three times per week, all p53-/- mice developed skin tumors by week 12. All the p53-/- mice developed multiple tumors by week 16. The majority of the tumors occurred on the ears. None of the p53+/+ mice developed skin tumors after 17 wk of UV exposure. Ten p53-/- tumors were examined histologically: five invasive squamous cell carcinomas, four squamous cell carcinomas in situ, and one actinic keratosis. p53-/- mice have a short life-span due to internal tumors or a deficiency in the immune system; however, ultraviolet B exposure did not significantly reduce the life-span of p53-/- mice. These results demonstrate that loss of wild-type p53 function shortens the latent period and predisposes the animals to the development of squamous cell carcinomas after ultraviolet irradiation.
Insights
Loss of the p53 gene accelerates skin tumor development in mice exposed to ultraviolet B radiation. These p53-deficient mice developed squamous cell carcinomas much faster than wild-type mice.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- The p53 gene plays a crucial role in preventing cancer formation.
- Mutations in the p53 gene are frequently observed in skin cancers induced by ultraviolet (UV) light.
Purpose of the Study:
- To investigate the role of the p53 gene in the development of skin cancer after chronic UV radiation exposure.
- To compare skin carcinogenesis in p53-deficient mice versus wild-type mice.
Main Methods:
- Mice with homozygous p53 deficiency (p53-/-) and wild-type p53 (+/+) mice were subjected to chronic ultraviolet B (UVB) exposure.
- Tumor development and latency periods were monitored.
- Histological examination of tumors was performed.
Main Results:
- All p53-/- mice developed skin tumors by week 12 and multiple tumors by week 16, predominantly on the ears.
- No skin tumors were observed in p53+/+ mice after 17 weeks of UVB exposure.
- Histological analysis revealed squamous cell carcinomas and actinic keratosis in p53-/- mice.
Conclusions:
- Loss of wild-type p53 function significantly shortens the latency period for skin tumor development following UVB irradiation.
- p53 deficiency predisposes mice to developing squamous cell carcinomas after UV exposure.
- UVB exposure did not significantly impact the already shortened lifespan of p53-/- mice.