Induction of cell cycle perturbations by the tear gas 2-chlorobenzylidene malonitrile in synchronously and asynchronously proliferating mammalian cells.

Abstract

The effects of the tear gas 2-chlorobenzylidene malonitrile (CS) on mammalian cell proliferation were studied in detail using bromodeoxyuridine/Hoechst flow cytometry. In synchronized (G0/G1-phase) Chinese hamster embryo (CHE) cells, exposure to CS (60 microM) caused a permanent arrest in the G0/G1 phase in 50% of the cells and a delayed G0/G1 phase exit. In asynchronously growing CHE cells, the CS-induced cell kinetic perturbations varied with the cell cycle stage during treatment. While G1-phase cells showed a delayed progression through S and G2/M phases, S-phase cells were mainly inhibited in the G2/M compartment of the first cell cycle. In contrast, CS-treated, asynchronous, amniotic fluid-derived, fibroblast-like (AFFL) cells exhibited a prolonged transit through the G2/M phase of the first cell cycle regardless of the cell cycle stage during treatment. This indicates that the induced cytotoxicity of CS is a function of both the cell cycle phase and the particular type of cells.