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Growth Fraction as the Major Determinant of Multicellular Tumor Spheroid Growth Rates¹

Cancer Research and Treatment Center and Department of Radiology, University of New Mexico, Albuquerque, New Mexico 87131

Multicellular tumor spheroids (MTS) from seven murine solid tumors have been compared in terms of their growth rate and the fraction of the cells that are in cycle. Growth rates ranged from a low of 19 µm/day through a maximum of 106 µm/day, demonstrating a far wider range of growth rates than is observed when the same tumors are grown as monolayers. Through the use of an [¹²⁵I]lodouridine deoxyribose incorporation assay, it has been possible to demonstrate that cells within the MTS that are in cycle double at a slower rate than they do in monolayers and that the depth of the dividing shell ranges from less than 20 to more than 100 µm. The depth of the dividing shell or the growth fraction is highly correlated with the MTS growth rate (r = 0.97). We conclude that the major factor that determines the wide range of MTS growth rates, in spite of relatively uniform doubling times in monolayer, is the fraction of the cells that are in cycle.

¹ Research supported by Grant 5-P01-CA-14052-04 and Contract NIH-N01-CB-74203 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Cancer Research and Treatment Center, University of New Mexico, 900 Camino de Salud, N. E., Albuquerque, N. M. 87131.

Received 8/17/77. Accepted 2/20/78.