Duration of Inhibition of Synthesis of DNA in Tumors and Host Tissues after Single Doses of Nitrosoureas

Single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-( trans -4-methylcyclohexyl)-1-nitrosourea caused transient inhibition of the incorporation of thymidine-3H into the acid-insoluble material of the liver, spleen, lungs, kidneys, and brains of normal and plasmacytoma-bearing hamsters and greater and longer lasting inhibitions of such incorporation into the acid-insoluble material of the tumors. In normal mice and mice bearing s.c.-implanted Lewis lung carcinoma, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-( trans -4-methylcyclohexyl)-1-nitrosourea caused transient inhibition of the incorporation of thymidine-3H by the lung and spleen, while there was little or no inhibition of such incorporation by the liver, kidney, and brain; inhibition of incorporation by the tumor was greater than that for the host tissues, and it endured throughout the period of the experiment. The observed greater inhibition by 1-(2-chloroethyl)-3-( trans -4-methylcyclohexyl)-1-nitrosourea is consistent with its reported greater therapeutic activity against the Lewis tumor. It is concluded that these agents damage some host tissues and the solid tumors but the host tissues recover from the damage more readily. It is not known whether the host tissues recover by repair within the damaged cells or by shedding or lysing the damaged cells and repopulating the tissues with healthy cells.