Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells

The cytotoxic activity of various chemotherapy agents was investigated in asynchronous populations of cultured 9L rat brain tumor cells, and as a function of their position in the cell cycle. Representative drugs from the classes of DNA-active agents, alkylating agents, spindle poisons, and antimetabolites were tested. The ability to induce cell lethality in asynchronous populations as a function of drug concentration varied for 1 hr pulse exposures. In order of decreasing cytotoxic activity, DHAQ was the most effective, followed by VCR, VDS, VBL, ADR, BCNU, cis-DDP, BLM, DBD, RZ, and HU. The effect of chemotherapy agents on synchronous 9L cells obtained by mitotic selection also varied with respect to the individual agent and was cell cycle-dependent. Survival age-responses ranged from being minimal to demonstrating significant fluctuations as a function of cell cycle position. For all agents except ADR and HU, the sensitivity of G1 phase was greater than S phase. RZ exhibited essentially a flat age-response. Comparison of the cell cycle age-responses of chemotherapeutic agents to those exhibited by the cytotoxic modalities of radiation and hyperthermia demonstrate several unique differences.