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Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35255
The graphs of observed pulse thymidine index against duration of emulsion exposure for seven experimental tumor systems have been observed to exhibit significant differences; either they were parallel and displaced, or they were nonparallel. The immediate practical consequence of this phenomenon is that identical emulsion exposure times, other experimental conditions being equal, may not be sufficient to provide valid comparison of thymidine indices among tumors. A mathematical model is described which relates observed autoradiographic labeling index to the distribution of radioactive atoms among individual cells that initially incorporate labeled material. Two distributions for uptake are considered, and the results are compared. One model assumes uniform uptake, and the other assumes that the number of radioactive atoms among cells acquiring label follows a
distribution. The
-distributed uptake model fits the observed thymidine index data for the seven tumors and may be expressed as Lj(t) = a[1 Qj(1 + bt)u] where Lj(t) is the labeling index for emulsion exposure duration of t, Qj is a polynomial, and a, b, and u are adjustable parameters. The counting threshold for scoring a cell as labeled is j and for j = 1, Q1 = 1. The model indicates that the labeling index should increase with the duration of emulsion exposure and that this increase is related to the proportion of "lightly" labeled cells. The parameter a is the maximum expected labeling index, and an estimate of this parameter should theoretically be independent of emulsion exposure time.
1 Supported by Contracts N01-CM-43756 and N01-CM-97309 from Drug Research and Development, Division of Cancer Treatment, National Cancer Institute, and Grant 1-R01-CA-25313-01 from National Cancer Institute, NIH. Department of Health, Education, and Welfare. Presented in part at the 68th Annual Meeting of the American Association for Cancer Research, Denver, Colo., May 18 to 21, 1977 (12).
2 To whom requests for reprints should be addressed at Southern Research Institute, 2000 Ninth Avenue, South, P.O. Box 3307-A, Birmingham, Ala. 35255.
Received 6/27/80. Accepted 11/ 5/82.
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