A Study of Comparative Protection against Lethality of Triethylenemelamine, Nitrogen Mustard, and X-Irradiation in Mice

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Abstract
A comparison was made of the protective action of cysteine, cysteamine, and sodium nitrite against the lethality in mice by X-irradiation, nitrogen mustard, or triethylenemelamine. Striking differences were revealed in the degree of protection obtained by the preadministration of the compounds. All compounds afforded some protection against the lethal effects of X-irradiation. Substantial protection against the lethality of HN2 was obtained with cysteine, and some protection with cysteamine. None of the compounds gave measureable protection against TEM. Chemical interaction of HN2 or TEM with cysteine or cysteamine in vitro was demonstrated. The reaction of HN2 with cysteine or cysteamine was instantaneous, whereas that between TEM and cysteine or cysteamine required several hours. The difference in reactivity may explain the differences in degree of protection afforded by the sulfhydryl-containing compounds. The in vitro reaction product of TEM with cysteine was isolated and purified. The probable structure of the reaction product is suggested. This compound was shown to be inert with respect to toxicity as well as carcinostatic effects on leukemia-1210. A threefold increase in the urinary excretion occurred when cysteine was preadministered to mice as compared to HN2 alone. A compound corresponding to the Rf of the reaction product appeared in this urine. The suggestion is made that the mechanism of cysteine protection is through direct chemical inactivation of HN2.