Diverse effects of ADP-ribosyl transferase inhibitors on G2 progression and lethality in Chinese hamster ovary cells damaged by DNA-interfering agents.

DNA-damaging agents used in this study could be divided into two groups, according to their ability to retard G2 traverse. One group included monofunctional alkylating agents, such as N-methyl-N-nitrosourea, dimethyl sulfate, and Streptozotocin. Cells treated with them, which at the tested doses only slightly affected cell cycle progression from the G2 phase to mitosis, were retarded in going through mitosis by subsequent treatment with adenosine diphosphate-ribosyl transferase (ADPRT) inhibitors, such as benzamide, 3-aminobenzamide, nicotinamide, and theophylline, but not by caffeine. Effects of caffeine on G2 progression could be distinguished from those of the other ADPRT inhibitors, and even from the effects of another methylxanthine, theophylline. In addition, the lethality of the monofunctional alkylating agents was markedly enhanced by all of the ADPRT inhibitors, including caffeine. The other group consisted of a variety of agents, including intercalators (Adriamycin and Actinomycin D), a radiomimetic agent, Bleomycin, and a bifunctional alkylating antibiotic, Mitomycin C. They prevented cells from going through mitosis to different degrees. The G2-prolonged cells were variously responsive to ability of the ADPRT inhibitors to release G2-arrest and to enhance cell death.