Clarke Davison

Metabolism of bis-β-chloroethyl sulfide (sulfur mustard gas)

Abstract The metabolism of bis-β-chloroethyl sulfide- 35 S has been investigated in mice, rats and human subjects. In the rodents, the major portion of radioactivity was excreted in the urine within the first 24 hr, whereas in the human considerable radiosulfur was retained for long periods. In the rat only traces of radioactivity were expired, while small amounts were found in the feces. Large amounts of thiodiglycol and of bis-β-chloroethyl sulfone have been detected in the urine, largely as conjugates. Evidence is presented that much of the drug reacts immediately with glutathione, and this complex is excreted. It is concluded that the majority of the radioactivity excreted in the urine represents compounds formed from alkylation by the drug, rather than metabolites formed by enzymic action.

Gastric hemorrhage induced by nonnarcotic analgetic agents in dogs.

The effect of various nonnarcotic analgetic agents in producing gastric hemorrhage has been investigated in Pavlov‐pouch dogs. Of the compounds tested, only aspirin in suspension at pH 3.0 produced extensive bleeding. The same drug in solution, as well as salicylic acid, salicylamide, methylsalicylate, and acetaminophen, produced no significant effect. Intravenous aspirin in high doses failed to cause gastric effects.

DISTRIBUTION AND FATE OF ALKYLATING AGENTS

Studies on the metabolism of alkylating agents have been prompted not only by the usual need to know more of their absorption, distribution, and excretion, but by the hope that such information may give some insight into their mechanism of action. A review of the early work on their pharmacology has been published (Philips, 1950). Because of their extremely high toxicity and the lack of methods sufficiently sensitive for their qualitative as well as quantitative determination, usually it has been necessary to synthesize these drugs with radioisotope labels. Selection of the proper label and its position in the drug molecule are important if one is to obtain results that will be useful in interpreting the mechanism of action.

Metabolism of Radioactive Para-Aminobenzoic Acid in an Escherichia coli Mutant.

Summary Radioactive p-aminobenzoic acid has been incubated with an x-ray mutant of Escherichia coli which requires this substance as a growth factor. By column chromatography 4 soluble radioactive fractions have been isolated from the cell bodies of the organism, none of them consisting of the original substrate. Two of the fractions possess citrovorum factor activity, but none of them are identical with folic acid, citrovorum factor or certain of its derivatives.