Pronounced damage of intestinal tract mucosa by the combination of 1-methyl-1-nitrosourea plus 1,3-bis-(2-chloroethyl)-1-nitrosourea. Effect of drug sequence and time interval of administration.

The combination of 1-methyl-1-nitrosourea (MNU) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has an overadditive toxicity in rats. This overadditive effect is dependent on drug sequence and time interval between the administration of both compounds. Application of MNU within 2 h prior to BCNU or simultaneous application of both compounds displayed the highest toxicity. The dose-limiting toxicity appears to be a severe damage of the intestinal mucosa.