The lethal activity and repair inhibition capacity of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea

Summary The survival response of human colorectal carcinoma cells treated in vitro for 1 h with PCNU was characterized by a threshold exponential curve, Dq = 8 g/ml (1 h) and D₀ = 22 g/ml (1 h). Continuous treatment induced decreasing degrees of cell kill although PCNU was biologically stable in solution for at least 24 h. Cells treated with PCNU were unable to recover from potentially lethal damage but were quite capable of repairing PCNU-induced sublethal damage. Thus, PCNU with different alkylating and carbamoylating than other nitrosourea congeners had similar cytotoxic and repair inhibition capacities. Any therapeutic gain in the clinical use of PCNU must derive only from its lipophilic properties and not from its superior activity at the cellular level.Abbreviations PCNU 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-1-nitrosourea (NSC 95466) - CCNU 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037) - BCNU 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC 409962) cis-acid, 4-(3-(2-chloroethyl)-3-nitrosoureido)-cis-cyclohexane-carboxylic acid (NSC 153174) - MeCCNU 1-(2-chloroethyl)-3-trans-(4-methyl-cyclohexyl)-1-nitrosourea (NSC 95441) - PE plating efficiency - Dq quasithreshold dose equal to the intercept with the abscissa (at 100% survival) of the exponential part of survival curve - D₀ mean lethal dose equal to the concentration required to reduce survival by 63% on exponential part of survival curve