C. J. Cheng, Shinji Fujimura, Dezider Grunberger
1972
Citations
1
Influential Citations
130
Citations
Quality indicators
Journal
Cancer research
Abstract
The macromolecular binding of radioactivity from 1-(2-chlorethyl)-3-cyclohexyl-1-nitrosourea, labeled with 14C in either the cyclohexyl moiety or the ethylene residue, was studied in the L1210 leukemia-bearing mice, in a suspension of L1210 leukemia cells, and during in vitro incubation with isolated nucleic acids and proteins. In all three systems, radioactivity from cyclohexyl-14C-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-14C-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-14C-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.