FOUNDATIONS OF THE USE OF AN ENZYME-KINETIC ANALOGY IN CELL-MEDIATED CYTO-TOXICITY

The **5**1Cr-release microcytotoxicity assay is often used to demonstrate and quantify the action of cytotoxic cell populations. The assay involves two main cell types, the effector cells (which contain the cytotoxic population) and the target cells (usually from a tumor or cell line). The target cells incorporate a radio label which is released both spontaneously and when the target is lysed by the cytotoxic cells. A mathematical model of the **5**1Cr-release microcytotoxicity assay is utilized to find conditions under which the kinetics of this assay resemble the kinetics of a classical enzyme-substrate reaction. Assuming a steady-state approximation, that ″bystander″ effector cells do not bind markedly better than the cytotoxic effector cells, and that the programming of the target cells for lysis is irreversible, it is shown that the velocity of label release is v equals v//m//a//xT//T/(K//1/////2 plus T//T), where both V//m//a//x and K//1/////2 are linear functions of the effector-cell population and T//T is the initial target-cell population . Moreover, the expressions of K//1/////2 and V//m//a//x are expressed in terms of natural kinetic parameters of the process and attributes of the noncytotoxic bystanders.