Dissociation of Sensitivities to Tumor Promotion and Progression in Outbred and Inbred SENCAR Mice

I. B. Gimenez-Conti, A. B. Bianchi, S. M. Fischer, J. J. Reiners, C. J. Conti, T. J. Slaga

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37 Scopus citations

Abstract

The sensitivity of outbred SENCAR mice and inbred SENCAR (SSIN) mice to multistage carcinogenesis was studied. Tumors were induced using either 7,12-dimethylbenz(a]anthracene or Nmethyl-N'-nitro-N-nitrosoguanidine as initiators and 12-O-tetradecanoylphorbol-13-acetate or benzoyl peroxide as promoting agents. Although the number of papillomas per mouse was higher in SSIN than in outbred SENCAR mice, the number of carcinomas observed in the SSIN strain was significantly lower regardless of the initiator or promoter used. It was also observed that the expression of markers of premalignant progression (i.e., dysplasia, expression of keratin K13, and loss of keratin Kl expression) was markedly suppressed in SSIN papillomas. After 50 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate, the pattern of expression of K13 and Kl in SSIN mice was comparable to the pattern observed in outbred SENCAR mice after 10 to 20 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate. It was also observed that 67% of the tumors induced in SSIN mice by initiation with 7,12-dimethylbenz|a]anthracene exhibited a mutation in codon 61 of the Ha-ras-1 gene. This latter finding suggests that the differences observed in tumor progression between the inbred strain and the outbred stock are not related to a genetic alteration in the Ha-ras-1 gene but rather to an independent event that we have postulated to involve a putative suppressor gene. The data reported here suggest that the putative gene(s) that confers susceptibility to tumor promotion was segregated from the gene(s) involved in tumor progression during selection and inbreeding of the SENCAR mouse stock.

Original languageEnglish (US)
Pages (from-to)3432-3435
Number of pages4
JournalCancer Research
Volume52
Issue number12
StatePublished - Jun 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gimenez-Conti, I. B., Bianchi, A. B., Fischer, S. M., Reiners, J. J., Conti, C. J., & Slaga, T. J. (1992). Dissociation of Sensitivities to Tumor Promotion and Progression in Outbred and Inbred SENCAR Mice. Cancer Research, 52(12), 3432-3435.