Cell-cycle-specific chromosome damage following treatment of cultured Chinese hamster cells with 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl

Abstract

The induction of chromosome damage in Chinese hamster (line CHO) cells by 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl (MAC) (NSC-141549) was studied in cell populations growing exponentially and at various stages of the cell cycle following release from isoleucine-deficient G1-arrest. Autoradiographic analysis demonstrated that cells in S-phase at time of drug addition (2 microgram MAC/ml for 2 hr) were delayed 8 hours before entering mitosis. Cells in G1 at the time of MAC treatment were not as severely delayed, which resulted in a rather sharp increase and decrease in a percent labeled mitosis curve. Chromosome damage occurred differentially during the cell cycle. Cells in late G2 during MAC treatment contained incompletely condensed chromosomes with occasional chromosome interchanges at the next mitosis. Early G2 cells were severely damaged (greater than 20 breaks/cell). Damage to cells in S or G1 at the time of MAC addition was less severe, whereas cells in G1-S traverse had intermediate levels of chromosome breaks. Thus MAC appeared to be particularly effective at times when chromatin was undergoing structural modifications (G1-S and S-G2 boundaries). Low concentrations of MAC (0.05 microgram/ml) increased the rate of sister chromatid exchange to almost eight times the background rate. The cellular effects of MAC were compared with previously reported studies of other antitumor agents.