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A Study of the Relationship between the Rate of Ethyl Carbamate (Urethan) Catabolism and Urethan Carcinogenesis

( Department of Experimental Biology, The Weixmann Institute of Science, Rehovoth, Israel)

An enzyme system capable of catabolizing carbonyl-C¹⁴-labeled ethylcarbamate to C¹⁴O₂ was demonstrated in mouse liver, lung, and skin breis. Three weak inhibitors of this catabolic activity were found among structural analogs of urethan tested in equimolar concentration.

Liver brei high-speed supernatant solutions, obtained from 6-month-old Swiss mice, were several times as active as similar preparations from 1- and 2-week-old mice. The concentration of urethan in the blood of 13-day-old and 6-month-old mice, at various times after injection of 0.75 mg urethan/gm, was determined. The catabolic rate in adult mice was approximately 1 times that in 13-day-old mice.

The relationship between the greater retention of urethan by young than by old mice and the greater response of younger mice to the carcinogenic action of urethan suggests that the length of time urethan remains in the body is a critical factor in determining tumor yield.

Received 8/ 5/59.