Effect of Antimetabolites on Kinetic Behavior of Proliferating Cultured L1210 Leukemia Cells2

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Abstract
The effect of amethopterin, 5-fluorouracil, 1-β-D-arabinofuranosylcytosine hydrochloride, and azaserine on the kinetic behavior of proliferating cultured L1210 leukemia cells was studied. Leukemia L1210 cells proliferating in vitro were exposed to selected drug concentrations for different periods and the number of cells surviving drug treatment was estimated by an animal. bioassay method. The cultured L1210 populations exhibited two distinct types of kinetic behavior relating to the rate of cell killing: 1) In L1210 populations treated with amethopterin,5-fluorouracil, and 1-β-D-arabinofuranosylcytosine hydrochloride, the rate of cell killing deviated from first-order kinetics. (The kinetics.could be described by a Gompertz equation of the form N = N0e-β/α(1-e-αt) where N0 is the number of viable cells present at time zero, N is the number of viable cells present at time t, t is the duration of drug exposure, β is the rate of population reduction, and a is a constant which expresses the rate of change of β.) The rate of population reduction appeared to depend, at least partly, on .the metabolic heterogeneity of the cell populations. 2) In L1210 cell populations treated with azaserine, the rate of viable. cell reduction followed first-order kinetics. In this case, a is not significantly different from zero, and the Gompertz equation reduces to N = N0e-βt which is the first-order rate equation. The rate of cell killing appeared to be independent of the metabolic heterogeneity of the cell populations.