CCPAO--cell cycle stage nonspecific cytotoxic agent

Experiments were carried out to determine the character of the cytotoxic effect of the newly-synthesized substance N,N-bis (2-chloroethyl)-3-chloropropionamidine oxalate (CCPAO). The experiments were carried out on EMT6 tumour cells in the plateau phase of culture growth. The cells were incubated with the drug for 1, 2 and 15 hours. The effect of the treatment was assessed by the change in the surviving cell fraction (SCF). The value of ID50 was determined for different patterns of treatment. The ID50 value was found to be relatively low after brief and prolonged incubation of the cells with the drug: 5.18 mg/kg (for 1 compared with 15 hours) and 7.72 mg/kg (for 2 compared with 15 hours). The analysis of the dose-effect curves for the brief and prolonged treatments revealed the existence of a similarity in the course, manifested as a decrease in SCF, parallel with a rise in the concentration of the drug. The data obtained indicate that CCPAO has a nonspecific character with respect to the cell cycle phases, suggesting that optimum therapeutic results can be expected in vivo when the drug is administered intermittently in high doses.