Malignant progression of mouse skin papillomas treated with ethylnitrosourea, N-methyl-N′-nitro-N-nitrosoguanidine, or 12-O-tetradecanoylphorbol-13-acetate

J. F. O'Connell, A. J.P. Klein-Szanto, D. M. Digiovanni, J. W. Fries, T. J. Slaga

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Mouse skin tumors were induced by a single topical application of 7,12-dimethylbenzanthracene (DMBA), followed by biweekly promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). After 20 weeks of promotion, mice were treated twice weekly for 2 weeks with either ethylnitrosourea (ENU), N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) or TPA. Thereafter all groups were treated biweekly with TPA. The ENU-treated group had a higher percentage of animals with carcinomas and developed 217% more cumulative carcinomas per group than TPA-treated controls. The percentage of mice with carcinomas and the cumulative number of carcinomas per group in MNNG-treated mice was higher than TPA-treated controls but was less than ENU-treated mice. The ratio of cumulative carcinomas to cumulative papillomas in ENU treated, MNNG-treated and TPA-treated mice was 16%, 9% and 6%, respectively. Histological examination of tumors remaining at the termination of the experiment revealed the presence of keratoacanthomas, some of which stained positive for γ-glutamyltransferase (GGT), in the ENU-treated and MNNG-treated, but not the TPA-treated groups. The fact that no new papillomas developed during the progression stage indicated that enhanced carcinogenesis resulted from the progression of pre-existing tumors. Enhanced progression of benign skin tumors in mice by only a few treatments of an agent may serve as a potential model for studies into the mechanisms and the inhibition of malignant progression. The model also allows for a comparison of the potency of agents in enhancing malignant progression.

Original languageEnglish (US)
Pages (from-to)269-274
Number of pages6
JournalCancer Letters
Volume30
Issue number3
DOIs
StatePublished - Mar 1986
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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