THE CELL-KILLING KINETICS OF ANTICANCER ANTIBIOTICS AND THE SENSITIVITY OF L-1210 MOUSE LEUKEMIA CELLS

Abstract

The cytocidal action of anticancer antibiotics has been quantitatively studied on the single cells of suspension-grown L-1210 mouse leukemia cells (L-1210/C), using soft agar cloning assay method.
The typical characteristics in the cytocidal action of anticancer antibiotics is the concentration-dependent action. The rate of cell killing can be described by the equation Cⁿ·T=K, where C is the concentration of antibiotics, T is the exposure time required to kill 90% of a cell population exposed at the concentration C, n is any positive number, and K is a constant. When L-1210/C cell population is treated with an antibiotic under a constant exposure time, the rate of cell killing can be described by a first-order kinetics log S=-k (D-a) , where S is surviving fraction, D is the concentration of antibiotics, and k and a are constant. The value of a means the concentration over which the cellkilling action appears, and the value of k means the population reduction rate. The sensitivity of L-1210/C cells can be indicated either by the 90% mean lethal dose (MLD₉₀), expressed by a reciprocal of slope coefficient k, showing the concentration of antibiotics needed to kill 90% of cells, or by the minimum inhibitory concentration for 10⁶ cells (MIC/10⁶) indicated by (6/k) +a.
The anticancer agents which have these characteristics are proposed to call type I agents, which are divided into two subtypes : type Ia agents that show the time-independent action with large n value (n>>1) in the equation Cⁿ·T=K and type Ib agents that show the time-dependent action with the unity of n value around 1. 40. The type Ia agents are neocarzinostatin and carzinophyllin. Many others such as mitomycin C, daunorubicin, adriamycin, chromomycin A-3, dactionomycin, bleomycin A-2 complex, and bleomycin A-5 belong to type Ib agents.