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Publication : The genetic control of chemically and radiation-induced skin tumorigenesis: a study with carcinogenesis-susceptible and carcinogenesis-resistant mice.

First Author  Pazzaglia S Year  2002
Journal  Radiat Res Volume  158
Issue  1 Pages  78-83
PubMed ID  12071806 Mgi Jnum  J:77153
Mgi Id  MGI:2181111 Doi  10.1667/0033-7587(2002)158[0078:tgcoca]2.0.co;2
Citation  Pazzaglia S, et al. (2002) The genetic control of chemically and radiation-induced skin tumorigenesis: a study with carcinogenesis-susceptible and carcinogenesis-resistant mice. Radiat Res 158(1):78-83
abstractText  Pazzaglia, S., Mancuso, M., Rebessi, S., Di Majo, V., Tanori, M., Biozzi, G., Covelli, V. and Saran, A. The Genetic Control of Chemically and Radiation-Induced Skin Tumorigenesis: A Study with Carcinogenesis-Susceptible and Carcinogenesis-Resistant Mice. Radiat. Res. 158, 78-83 (2002). Outbred carcinogenesis-resistant (Car-R) and carcinogenesis-susceptible (Car-S) mouse lines were generated by phenotypic selection for resistance or susceptibility to two-stage skin carcinogenesis. These two Car mouse lines differ by >100-fold in susceptibility. In the present study, we tested the hypothesis that a subset of genetic loci responsible for susceptibility or resistance to chemical skin tumorigenesis may also be involved in radiation-induced skin tumorigenesis. Skin tumorigenesis was tested in groups of Car-S/R mice after X-ray initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. We found that ionizing radiation can initiate skin tumors in Car-S mice but not in Car-R mice. In Car-S mice, the most effective radiation doses (6 and 10 Gy given in four fractions) gave a threefold increase in tumor multiplicity and a twofold increase in tumor incidence compared to a TPA-only control group. We performed a molecular analysis of Hras gene mutations in skin tumors of Car-S mice induced by X-ray initiation/TPA promotion or by TPA promotion alone. The most notable difference emerging from the comparison of these mutation patterns is the high incidence ( approximately 50%) of papillomas lacking Hras gene mutations in X-ray-initiated/TPA-promoted papillomas compared to 13% in papillomas induced by TPA alone, suggesting that lack of Hras gene mutations is a consistent feature of radiation-induced papillomas.
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