SOME STRUCTURAL REQUIREMENTS FOR THE PREVENTION OF LEUKOPENIA INDUCED BY NITROGEN MUSTARD 12

Abstract

Admn. of L-cysteine to animals prior to the injn. of nitrogen mustard (HN2) modifies the severe leukopenia induced by HN2. The specificity as well as the mechanism of L-cysteine protection was investigated by correlating the chemical structure of closely related compounds with their ability to prevent HN2-induced leukopenia in rabbits. Several amino acids and sulfhydryl-containing compounds structurally closely related to cysteine, as well as compounds containing various combinations of functional sulfhydryl, amino and carboxyl groups were investigated. Ascorbic acid was also tested because, like the other compounds, it is a strong reducing agent. Of the compounds studied, only those with vicinal sulfhydryl, amino and carboxyl groups were capable of modifying HN2-induced leukopenia. L-cysteine, which has a free sulfhydryl, amino and carboxyl groups on adjacant C atoms was the most effective. D,L-Homocysteine and glutathione were less effective. Substitution or alteration of either the free sulfhydryl, amino or carboxyl group results in complete disappearance of any detectable protective effect. Under the conditions of the expts., neither the reducing action of a compound, nor the presence by themselves of free sulfhydryl, amino or carboxyl groups can be correlated with the potency of a compound to prevent HN2-induced leukopenia. The data indicate that the protective effect of L-cysteine and its homologs does not result from inactivation of HN2. L-Cysteine and related compounds may protect some substance(s) essential for leukopoiesis from destruction by HN2.