Urethan carcinogenesis and nucleic acid metabolism: in vitro interactions with enzymes.

In the light of suggestions in the literature linking the car cinogenic action of urethan (ethyl carbamate) with the inhibi tion of an enzymatic step in nucleic acid metabolism (par ticularly pyrimidine synthesis), a series of enzymes has been assayed in vitro at concentrations of urethan which are supralethal in mice. These enzymes were: ornithine transcarbamylase; the enzymes leading to the synthesis of orotic acid, viz., carbamyl phosphate synthetase, aspartate transcarbamylase, dihydroorotase, and dihydroorotate dehydrogenase ; DNA and RNA methylase; DNA, RNA, and polyriboadenylate polymerase; alkaline and acid deoxyribonuclease ; alkaline and acid phosphatase and snake venom phosphodiesterase. The ability of urethan to interfere with the induction of jS-galactosidase in Escherichia coli was also investigated. Nucleic acid methylases were found to be inhibited by ure than in high concentrations; the final urethan concentrations necessary for 50% inhibition ranged from 0.07 to 0.25 M. No significant inhibition of any of the enzyme systems tested was found when they were assayed at a final urethan concentration of 0.06 M. Since this concentration is more than double the lethal concentration for mice, it was concluded that no bio logically significant inhibition of nucleic acid metabolism by urethan has yet been demonstrated.