Response of exponentially growing, stationary-phase, and synchronized cultured human colon carcinoma cells to treatment with nitrosourea derivatives.
The lethal effects of two nitrosourea derivatives, 1,3-bis(2-chloroethyl)-1-nitrosourea and 4-[3-(2-chloroethyl)-3-nitrosoureido]-cis-cyclohexanecarboxylic acid, on a continuous line of human colon carcinoma cells (LoVo cells) were investigated. The survival response of exponentially growing and stationary-phase LoVo cells to both drugs were of the threshold exponential type. Survival was identical whether drugs were dissolved in medium or in Hanks' balanced salt solution. In contrast to previous results obtained for human lymphoma cells, 1,3-bis(2-chloroethyl)-1-nitrosourea exerted a progressively greater killing effect on LoVo cells as the incubation time was prolonged, while 4-[3-(2-chloroethyl)-3-nitrosoureido]-cis-cyclohexane-carboxylic acid, under similar circumstances presented decreased lethality in comparison to both 1,3-bis(2-chloroethyl)-1-nitrosourea and the effect previously observed for the lymphoma cells. Although no recovery from potentially lethal damage was noted for both exponentially growing and stationary-phase cells treated with each agent, in split-dose experiments, LoVo cells were able to recover from sublethal damage. No significant cell cycle stage dependent differences in killing ability were observed for the two agents.