Comparison of Two-Stage Epidermal Carcinogenesis Initiated by 7,12-Dimethylbenz(a)anthracene or N-Methyl-N'-nitro-N'-nitrosoguanidine in Newborn and Adult SENCAR and BALB/c Mice

Henry Hennings, Deborah Devor, Martin L. Wenk, Thomas J. Slaga, Brigitte Former, Nancy H. Colburn, G. T. Bowden, Stuart H. Yuspa, Kjell Elgjo

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115 Scopus citations

Abstract

In order to define factors which determine susceptibility to chemical carcinogenesis, mice sensitive (SENCAR) and resistant (BALB/c) to epidermal carcinogenesis were studied under several treatment conditions for sensitivity to initiation by 7,12-dimethylbenz(a)anthracene or N-methyl-N‘-nitro-N-nitrosogua-nidine and promotion by 12-O-tetradecanoylphorbol- 13-ace-tate. In newborns of both strains, topical application of initiator was much less effective than in adults. However, initiation by i.p. injection of 7,12-dimethylbenz(a)anthracene is at least as effective in newborns as in adults, which may indicate that topically applied carcinogen is not delivered effectively to target cells in newborns. Thus, newborn epidermis can respond to 7,12-dimethylbenz(a)anthracene as well as adult epidermis when the initiator is appropriately administered. SENCAR mice are much more sensitive than are BALB/c mice to both initiators, which suggests that enhanced metabolic activation of hydrocarbon carcinogens by SENCAR mice is unlikely to account for their sensitivity. Newborn male SENCAR's developed approximately 50% more papillomas than did females in all groups. BALB/c newborn mice developed so few tumors that a meaningful comparison of sensitivity of males and females could not be made. Thus, the increased sensitivity of SENCAR's was apparent regardless of route of administration of initiator or the age or sex of the mice. SENCAR mice also developed a significant number of papillomas and squamous cell carcinomas with 12–0-tetradecanoylphorbol-13-acetate promotion in the absence of an exogenous initiator. Therefore, the skin of SENCAR mice may contain an initiated population of cells capable of responding to tumor promoters.

Original languageEnglish (US)
Pages (from-to)773-779
Number of pages7
JournalCancer Research
Volume41
Issue number3
StatePublished - Mar 1 1981
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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