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Effects of 7-R-O-Methylnogarol (Menogaril) on L1210 Cell Progression in Vitro and in Vivo

Cancer and Viral Diseases Research, The Upjohn Company, Kalamazoo, Michigan 49001

Menogaril (7-R-O-methylnogarol) is an anthracycline which has significant antitumor activity in vivo and is in Phase II clinical trial. We report here the drug effect on growth and cell cycle progression of L1210 mouse leukemia cells in vitro and in vivo. At doses which inhibited the growth of L1210 cells in vitro, menogaril slowed the progression of cells through S phase and blocked cells in G₂ + M. 7-R-O-Methyl-N-demethylnogarol, the major metabolite of menogaril had the same effects on cell progression in vitro. Menogaril effect on cell progression in vivo was studied with peritoneal L1210 ascites growing in CD2F₁ mice. Early in infection, i.e., 3 days after inoculation of 10⁵ L1210 cells, DNA histograms of cells from control and drug-treated mice showed only a G₁ peak. This presumably represented host diploid G₀–G₁ cells which predominated in the peritoneal cavity and masked the histogram of L1210 cells. Later in infection, when about 10⁸ or more cells were present in the ascites, L1210 cells predominated and DNA histograms were representative of L1210 cells. When menogaril was injected at this time, the cell cycle effects were similar to those seen in vitro. Therefore, the L1210 in vivo model can be used to study cell progression effects only late in infection (when L1210 cells predominate), and due consideration should be given to contamination of the L1210 cells with host G₀–G₁ cells.

¹ To whom requests for reprints should be addressed, at Cancer and Viral Diseases Research, The Upjohn Company, Kalamazoo, MI 49001.

Received 5/13/85. Revised 7/16/86. Accepted 8/11/86.