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 (∼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. © 2002 by Radiation Research Society.
|Pages (from-to)||78 - 83|
|Number of pages||6|
|Publication status||Published - 2002|
All Science Journal Classification (ASJC) codes
- Radiology Nuclear Medicine and imaging
Pazzaglia, S., Mancuso, M., Rebessi, S., Di Majo, V., Tanori, M., Biozzi, G., ... Saran, A. (2002). The genetic control of chemically and radiation-induced skin tumorigenesis: A study with carcinogenesis-susceptible and carcinogenesis-resistant mice. Radiation Research, 158(1), 78 - 83. https://doi.org/10.1667/0033-7587(2002)158[0078:TGCOCA]2.0.CO;2