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

Simonetta Pazzaglia, Mariateresa Mancuso, Simonetta Rebessi, Vincenzo Di Majo, Mirella Tanori, Guido Biozzi, Vincenzo Covelli, Anna Saran

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6 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)78 - 83
Number of pages6
JournalRadiation Research
Volume158
Issue number1
DOIs
Publication statusPublished - 2002
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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