A Possible Anti-folic Acid Effect of Urethane

Abstract

URETHANE (ethyl carbamate) is a compound with a series of diverse biological actions including narcotic effects, cytotoxic and cytostatic action, and remarkably varied carcinogenicity in different species and organs^1,2. The metabolic changes associated with these different activities are difficult to visualize since the compound is rapidly metabolized, being almost entirely eliminated within 24 h (ref. 3). In recent investigations by one of us⁴, it was demonstrated that an abnormal purine derivative can be demonstrated in the RNA from the livers of mice treated with ethyl-1-¹⁴C urethane. In the course of hypothetical consideration of possible pathways of action of urethane we considered the possibility that the acute effects observed might be due to an anti-folic acid effect. The acute biological effects of this compound are certainly similar to effects seen with folic acid antagonists such as aminopterin⁵; however, there is obviously no similarity in chemical structure. It was, nevertheless, decided to test the hypothesis in the following simple experiment.