Tumor cell kinetics in mixed populations

The delayed biopsy, relative movement method provides a rapid estimate of in situ potential doubling times in human tumors. The accuracy of the estimate, however, can be adversely influenced by normal diploid cells that are present in tumor biopsy specimens and have DNA profiles that overlap their tumor cell counterparts. Interference with the measurement of tumor cell kinetic parameters can result, the magnitude of which depends upon the DNA index and the proportion and labeling index of these normal cells. Two approaches that address this problem were explored in vitro: (1) A normal cell subtraction method was developed in which adjacent normal tissue and tumor are biopsied concurrently and are separately processed for flow cytometric analysis. Results are integrated to allow an approximate correction for the normal, diploid population's perturbation of the measurement of tumor labeling index and relative movement. This approach was examined in this present study through extensive testing in mixtures of various proportions of two in vitro cell lines. (2) The percent S phase method, developed by Durand, was examined in these same population mixtures, as well as separately in each population. Both methods provide reliable estimates of kinetics in mixed in vitro populations. The relative advantages and disadvantages of each, as well as the potential limitations if extended to in vivo measurements, are discussed.