Interaction of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037) with nucleic acids and proteins in vivo and in vitro.

SUMMARY The macromolecular binding of radioactivity from 1-(2-chiorethyl)-3-cyclohexyl-1-nitrosourea, labeled with ‘@ C in either the cyclohexyl moiety or the ethylene residue, was studied in the L1210 leukemia-bearing mice, in a suspension of Ll2lO leukemia cells, and during in vitro incubation with isolated nucleic acids and proteins. In all three systems, radioactivity from @ C-labeled 1-(2-chloroethyl). 3-cyclohexyl-1-nitrosourea was extensively bound to proteins, and there was negligible binding to nucleic acids. Radioactivity from the ethylene-' 4C-labeled drug was bound to both nucleic acids and proteins, but the binding was only a fraction of the observed protein binding of the cyclohexyl label. Of the various macromolecules examined for in vitro binding, poly-L-lysine and albumin were the most active in binding the cyclohexyl-labeled material; polyguanylic acid, polycytidylic acid, and tRNA were the most active in binding-the ethylene-' @ C-labeled material. The possibility that the carcinostatic activity of this drug reflects a dual capacity, namely, modification of cellular proteins via cyclohexylcarbamoylation and of nucleic acids via alkylation, is discussed.