Experimental evaluation of potential anticancer agents VIII. Effects of certain nitrosoureas on intracerebral L1210 leukemia.

Summary In quantitative therapeutic studies 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC-409962) and 1-(2-chloroethyl)-1-nitrosourea (NSC-47547) have been shown to have marked activity against intraperitoneal (I.P.) L1210 leukemia when administered by the I.P., subcutaneous, or oral route. This class of compounds is the first to be observed to possess an encouraging degree of activity against intracerebrally inoculated L1210 leukemia. Of the “active” derivatives of 1-methyl-1-nitrosourea studied to date, only those which have a higher degree of lipoid solubility and are essentially not ionized have shown capacity to affect intracerebral (I.C.) L1210 leukemia. Evidence has been obtained which suggests that the mechanism of action (at the biochemical level) of 1-methyl-1-nitrosourea and 1,3-bis(2-chloroethyl)-1-nitrosourea may be similar to that of certain well known alkylating agents. Experiments with bilateral implants of an alkylating agent-sensitive and -resistant plasmacytoma in hamsters showed the latter tumor to be cross-resistant to these compounds.