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Sensitivity to 1,3-Bis(2-chloroethyl)-1-nitrosourea and 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea of the EMT6 Tumor in Vivo as Determined by both Tumor Volume Response and in Vitro Plating Assay

Medical Research Council Clinical Oncology and Radiotherapeutics Unit, The Medical School, Hills Road, Cambridge, England

Measurements of the response of the EMT6 mouse tumor to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea by either tumor volume or the in vitro assay of the cell surviving fraction give very different results. For BCNU very little delay in tumor growth is caused by high doses of the drug, whereas the surviving fraction assayed 2 hr after drug administration may be as low as 10^-4 for comparable drug doses. Over the first 48 hr after BCNU, the measured surviving fraction in small tumors increases 50- to 100-fold; this is ascribed to the phenomenon known as "recovery from potentially lethal damage." For 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, however, this early rapid recovery in surviving fraction does not occur. Although the surviving fractions measured 24 hr after drug administration are similar for equivalent doses of the two drugs, the growth delay induced is very much longer for 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea than for BCNU. Neither of the agents appears to cause any increase in the rate of cell loss from tumors as measured by [¹²⁵I]iododeoxyuridine.

Received 12/27/77. Accepted 5/10/78.