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Murine Pulmonary Adenoma Bioassay of Potentially Effective Agents against Slow-growing Solid Tumors

Jeffrey C. Theiss, Gary D. Stoner and Michael B. Shimkin
Jeffrey C. Theiss
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Gary D. Stoner
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Michael B. Shimkin
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DOI:  Published January 1977
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Summary

An in vitro-in vivo system for screening potentially effective drugs against solid tumors is described. Drug toxicity to plateau-phase pulmonary adenoma cells is used as an in vitro screen for potential activity against solid tumors, since both plateau phase cultured cell populations and solid tumors are composed predominantly of nondividing cells. The effect of drugs with in vitro activity on the rate of appearance of urethan-induced adenomas on the lung surface of strain A mice in vivo is used to assess drug efficacy in the treatment of solid tumors, taking into consideration drug toxicity to and drug metabolism by the host. Arabinosylcytosine and hydroxyurea were ineffective against plateau phase cells in vitro, even at high concentrations (5 to 10 mg/ml), and did not affect pulmonary adenoma growth in vivo, even at toxic doses (arabinosylcytosine, 80 mg/kg; hydroxyurea, 800 mg/kg), as would be expected with these cell cycle-active drugs. Adriamycin, an effective agent against human solid tumors, was cytotoxic to plateau phase cultured cells (0% survivors at 1 µg/ml), and a dose of 2 mg/kg completely inhibited pulmonary adenoma growth in mice. Thus, this pulmonary adenoma bioassay would appear to effectively select for drugs which may be active against solid tumors in humans.

Footnotes

  • ↵1 This research was supported by Grant R01-CA-17877 and Contract NO1-CP-3-3232 from the National Cancer Institute.

  • Received June 24, 1976.
  • Accepted October 18, 1976.
  • ©1977 American Association for Cancer Research.
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January 1977
Volume 37, Issue 1
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Murine Pulmonary Adenoma Bioassay of Potentially Effective Agents against Slow-growing Solid Tumors
Jeffrey C. Theiss, Gary D. Stoner and Michael B. Shimkin
Cancer Res January 1 1977 (37) (1) 305-309;

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Murine Pulmonary Adenoma Bioassay of Potentially Effective Agents against Slow-growing Solid Tumors
Jeffrey C. Theiss, Gary D. Stoner and Michael B. Shimkin
Cancer Res January 1 1977 (37) (1) 305-309;
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Cancer Research Online ISSN: 1538-7445
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