Enhanced in Vitro Proliferation and in Vivo Tumorigenic Potential of Mammary Epithelium from BALB/c Mice Exposed in Vivo to 7-Radiation and/or 7,12-Dimethylbenz[a]anthracene

Laurel M. Adams, Stephen P. Ethier, Robert L. Ullrich

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Abstract

Virgin female BALB/c mice were exposed in vivo to whole body 7-radiation and/or to 7,12-dimethylbenz[a]anthracene (DMBA) p.o. Mammary epithelial cells were isolated and assayed for carcinogen altered cell populations both in vitro by an epithelial focus assay and in vivo by injection into cleared fat pads of syngeneic host mice. Five groups of mice were exposed as follows: (a) sham controls; (b) 50-rad 7-radiation; (c) 100-rad γ-radiation; (d) 75 μg DMBA; or (e) 50-rad 7-radiation followed in 1 week by 75 μg DMBA. Mammary epithelial cells were isolated and assayed at 24 h and at 1, 4, 16, and 52 weeks after in vivo exposure. Four to 12 mice per treatment per time point were individually assayed. Altered in vitro growth potential was characterized by the proliferation of carcinogen exposed (but not control) cells as epithelial foci which persisted at least 12 weeks in primary culture. Epithelial foci which could then be subcultured at least four times were termed subculturable epithelial foci. Altered in vivo morphogenic potential was characterized by dysplastic or neoplastic growth in host fat pads. With increased time in situ between exposure and assay, cell populations emerged which exhibited both increased in vitro subculturability and enhanced tumorigenic potential including a host response upon injection in vivo. Further, combined radiation and DMBA resulted in higher frequencies of subculturable epithelial foci than either treatment alone. The relevance of these progressive cellular changes to the process of mammary tumor development is discussed.

Original languageEnglish (US)
Pages (from-to)4425-4431
Number of pages7
JournalCancer Research
Volume47
Issue number16
StatePublished - Aug 1987

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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