Evaluation of the role of isocyanates in the action of therapeutic nitrosoureas

The half-lives of chloroethyl and cyclohexyl isocyanate have been determined in tissue culture medium, and the isocyanate concentration produced during the breakdown of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) has been calculated. L1210 or HeLa cells exposed either to the parent nitrosourea or to an equivalent constant isocyanate concentration show no deficiency in the repair of gamma-irradiation damage as measured by DNA strand separation in alkali. Viability studies indicate that the isocyanates play a minor role in the overall cytotoxicity of the nitrosoureas.