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Alterations in the DNA Metabolism of MCa-11 Mouse Mammary Tumor Cells Grown in Vivo and in Vitro¹

Department of Surgery, The University of New Mexico and the Albuquerque Veterans Administration Medical Center, Albuquerque, New Mexico 87108 [D. C. A., S. A., P. F. R.]; Los Alamos National Laboratory, Los Alamos, New Mexico 87544 [J. M.]; and Robertson Electronics, Albuquerque, New Mexico 87123 [J. R.]

Mouse mammary carcinoma (MCa-11) cells were grown in vitro in exponential, plateau-fed, and starved monolayer cultures or as 100-, 250-, and 500-µm tissue culture spheroids, and in vivo as small (4-mm diameter) and large (12-mm diameter) tumors. In all of these forms, the growth rates of the MCa-11 cells were found to decrease after an initial rapid proliferation of a relatively small number of cells. The DNA distributions of these cells during different rates of growth in vitro and in vivo, as well as the proportion and intensity of labeling of the S-phase cells with [³H]thymidine and [³H]deoxyuridine, were measured by flow and absorption cytometry. We found that significant numbers of MCa-11 cells remained in S phase, even after the growth rates in vivo and in vitro had slowed. However, as growth rates decreased, the intensity and proportion of S-phase cells labeled with exogenous DNA precursors decreased. We conclude that progressive alterations, including possible slowing and cessation, of replicative DNA synthesis occur in S-phase tumor cells as the metabolic constraints on tumor growth are increased.

¹ Supported by the Veterans Administration.

² Present address: Department of Surgery, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21205. To whom requests for reprints should be addressed.

Received 12/31/85. Revised 4/ 8/86. Accepted 5/ 2/86.

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