Inhibition of DNA repair by the 1,3-bis(2-chloroethyl)-1-nitrosourea breakdown product, 2-chloroethyl isocyanate.

The rate of rejoining of DNA strand breaks in L1210 cells exposed to X-irradiation has been studied using a recently developed technique for estimating DNA chain length: alkaline elution of prelabeled DNA through membrane fil ters. A marked inhibition of repair of single-strand breaks, has been produced by 2-chloroethyl isocyanate, a break down product in the decomposition of the antitumor agent l,3-bis(2-chloroethyl)-l-nitrosourea. No repair inhibition was produced by 2-chloroethylamine, or by hydroxyurea, actinomycin D, or cycloheximide. It is tentatively suggested that the cytocidal effect of 1,3-bis(2-chloroethyl)-l-nitrosourea, generally attributed to its alkylating activity, may be potentiated by one of its metabolites, 2-chloroethyl iso cyanate, through an inhibition of the repair of damaged DNA.