The Reactions of Chloroquine Mustard (CQM) and Nitrogen Mustard (HN2) with Ehrlich Cells*t

By incubating Ehrlich cells with isotopically labeled nitrogen mustards the relation between the extent of alkylation of cell constituents and the reduction of growth potential can be studied. Data obtained by such studies show that both CQM and HN2 react with a wide variety of cell constituents. Of the macromolecular constituents, the proteins undergo the greatest amount of alkylation, but the RNA shows the highest specific uptake of both agents. Chemical differences between CQM and HN~ are reflected in the greater in vivo alkylation of the DNA by the 4-aminoquinoline mustard. At equal concentrations of agent, HN~ is more effective in producing cell damage; conversely, equivalent cell damage is noted when alkylation of cell constituents by CQM is 5 times greater than that by HN~. Particularly in view of the disparity between the alkylation of DNA and the extent of cell damage, consideration is given to the ways in which the specificity of alkylation of particular sites on DNA might produce the observed results.