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

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 ob served to possess an encouraging degree of activity against intracerebrally inoculated L1210 leukemia. Ofthe “active― d rivatives of 1-methyl-1-nitrosourea studiedto date,onJ@y 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.