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Tumorigenesis in athymic nude mouse skin by chemical carcinogens and ultraviolet light
Abstract:
A variety of established skin tumorigenesis protocols were tested for efficacy on athymic nu/nu mice (BALB/c background) and compared on euthymic nu/+ counterparts. Chemical carcinogens and UV light were applied to the ears of 10 mice of each sex and genotype for each group. Treatments were: 0.5 mg 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] to each ear; 0.125 mg DMBA to each ear, followed by 0.1 microgram 12-O-tetradecanoylphorbol-13-acetate [(TPA) CAS: 16561-29-8] twice weekly for 56 weeks; 0.2 mg N-nitroso-N-methylurea [(NMU) CAS: 684-93-5; 1% in acetone, 20 microliter] to each ear; 0.1 mg NMU to each ear weekly for 30 weeks; 0.2 mg NMU to each ear, followed by TPA twice weekly for 56 weeks; two ip doses of N-nitroso-N-ethylurea [(NEU) CAS: 759-73-9; 25 mg/kg each], followed by TPA twice weekly topically for 56 weeks; and exposure to sunlamps (250- to 400-nm emission) two or three times per week for 20 weeks, for a total dose of 3.7 X 10(5) J/m2. The chemical treatments caused mainly squamous papillomas and carcinomas, sebaceous adenomas and adenocarcinomas, and basal cell tumors, which appeared both on the skin of the ears and elsewhere. UV light caused squamous tumors, basal cell tumors, and sarcomas. Ear skin of the nu/nu mice developed significantly more squamous tumors than those of nu/+ mice after DMBA-TPA, NMU-TPA, NEU-TPA, repeated NMU, or UV light. Similar results were obtained for the skin of the heads and bodies. Even a single dose of NMU caused a few tumors on the nude, but not the euthymic, mice. A single dose of DMBA caused primarily sebaceous adenomas, distributed at random over the entire bodies. These results show that, contrary to previous reports, nude mice are sensitive to skin tumorigenesis, more so than euthymic nu/+ mice similarly exposed to diverse types of carcinogen and treatment protocols.
Insights
Nude mice (nu/nu) are more susceptible to skin tumorigenesis than euthymic mice (nu/+) when exposed to various chemical carcinogens and UV light. These findings challenge previous assumptions about nude mouse sensitivity to skin cancer development.
Area of Science:
- Oncology
- Dermatology
- Immunology
Background:
- Athymic nu/nu mice are commonly used in cancer research but their sensitivity to skin tumorigenesis is debated.
- Established protocols for inducing skin tumors in mice were utilized for comparison.
- Understanding the immune status and carcinogen response is crucial for preclinical models.
Purpose of the Study:
- To evaluate the efficacy of various skin tumorigenesis protocols in athymic nu/nu mice.
- To compare the susceptibility of nu/nu mice versus euthymic nu/+ mice to chemically and UV-induced skin cancers.
- To determine if nude mice are more sensitive to skin carcinogenesis than their euthymic counterparts.
Main Methods:
- Athymic nu/nu and euthymic nu/+ mice (BALB/c background) were subjected to established chemical carcinogen (DMBA, NMU, NEU, TPA) and UV light treatments.
- Treatments included topical applications, single doses, and combinations over extended periods (20-56 weeks).
- Tumor incidence and types (squamous cell, basal cell, sebaceous, sarcomas) were documented on ears, heads, and bodies.
Main Results:
- Nude mice exhibited significantly higher incidences of squamous tumors compared to euthymic mice following DMBA-TPA, NMU-TPA, NEU-TPA, repeated NMU, and UV light exposure.
- Single doses of NMU induced tumors in nude mice but not euthymic mice.
- DMBA induced sebaceous adenomas across the bodies of nude mice.
- UV light induced squamous tumors, basal cell tumors, and sarcomas in both genotypes, with higher rates in nu/nu mice.
Conclusions:
- Contrary to previous reports, athymic nu/nu mice are sensitive to skin tumorigenesis.
- Nude mice demonstrate increased susceptibility to diverse carcinogen-induced skin cancers compared to euthymic mice.
- This study highlights the utility of nude mice as a more sensitive model for skin carcinogenesis research.