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Tumor copromoting activity of gamma-interferon in the murine skin multistage carcinogenesis model
1University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957.
Abstract:
Recombinant DNA-derived murine gamma-interferon (rMuIFN-gamma) was tested in the murine skin multistage carcinogenesis model as a modulator of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. Female SENCAR mice were topically initiated with 7,12-dimethylbenz(a)anthracene and promoted twice weekly with TPA for 20 weeks. Intraperitoneal administration of rMuIFN-gamma 1 day prior to TPA treatment affected neither the kinetics of papilloma development nor the percentage of mice that developed tumors. However, papilloma multiplicities could be either inhibited or increased depending upon the dose of rMuIFN-gamma. Papilloma multiplicities for mice receiving 100, 500, 1000, and 5000 units of rMuIFN-gamma were 184, 122, 105, and 84% of TPA control values, respectively. In contrast, twice weekly i.p. treatments of 7,12-dimethylbenz(a)anthracene initiated mice with only rMuIFN-gamma for 20 weeks did not promote the development of any tumors. Consequently, TPA functioned as a copromoter in those situations in which combined TPA and IFN-gamma treatments elevated papilloma multiplicities. Collectively, the current study demonstrates that rMuIFN-gamma can systemically modulate TPA-dependent promotion in mouse skin.
Insights
Recombinant murine gamma-interferon (rMuIFN-gamma) modulated skin tumor development in mice. Depending on the dose, rMuIFN-gamma either inhibited or increased papilloma multiplicities, showing its role in carcinogenesis promotion.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- The murine skin multistage carcinogenesis model is a standard for studying tumor promotion.
- 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent tumor promoter used in this model.
- Interferons (IFNs) are known immunomodulators with potential roles in cancer development.
Purpose of the Study:
- To investigate the effect of recombinant murine gamma-interferon (rMuIFN-gamma) on TPA-induced skin carcinogenesis in mice.
- To determine if rMuIFN-gamma acts as a modulator of tumor promotion in this model.
- To explore the dose-dependent effects of rMuIFN-gamma on papilloma development.
Main Methods:
- Female SENCAR mice were initiated with 7,12-dimethylbenz(a)anthracene.
- Mice were promoted twice weekly with TPA for 20 weeks.
- Intraperitoneal administration of varying doses of rMuIFN-gamma was given prior to TPA treatment.
Main Results:
- rMuIFN-gamma did not alter the kinetics or incidence of papilloma development.
- Papilloma multiplicities were dose-dependently inhibited or increased by rMuIFN-gamma.
- High doses of rMuIFN-gamma (5000 units) reduced papilloma multiplicity to 84% of control values.
- rMuIFN-gamma alone did not promote tumor development, indicating TPA's role as a copromoter when combined.
Conclusions:
- rMuIFN-gamma can systemically modulate TPA-dependent skin tumor promotion in mice.
- The effect of rMuIFN-gamma on carcinogenesis is dose-dependent.
- TPA acts as a copromoter in conjunction with rMuIFN-gamma to influence tumor development.