Carcinogenicity of Epoxides, Lactones, and Peroxy Compounds. IV. Tumor Response in Epithelial and Connective Tissue in Mice and Rats2

Abstract

The carcinogenic potencies of a series of alkylating and peroxy compounds were compared by the use of various routes of administration in mice and rats. Twelve of these compounds, earlier tested on mouse skin, were tested by one or more of the following routes: subcutaneous injection in mice and rats and intragastric feeding in rats. These experiments showed that those compounds tumorigenic to mouse skin are also active by other routes. These compounds are: β-propiolactone, β-butyrolactone, d,l-diepoxybutane, glycidaldehyde, and 1,2,5,6-diepoxyhexane. Those compounds inactive on mouse skin are weakly active or inactive by other routes. These compounds are: cumene hydroperoxide, 9,10-epoxy-stearic acid, diketene, 2,2,4-trimethylhydroxypentenoic acid-β-lactone, cyclohexenehydroperoxide, and lauroyl peroxide. β-Propiolactone and β-butyrolactone are mouse-skin carcinogens and induce gastric cancers when fed repeatedly to rats; however, 3 epoxides carcinogenic to mouse skin (glycidaldehyde, d,l-diepoxybutane, and 1-ethyleneoxy-3,4-epoxy cyclohexane) do not induce gastric cancers in rats. This finding is related to the rapid acid-catalyzed hydrolysis of epoxides in the rat stomach. The compounds tested induced tumors mainly at the site of application and did not give any significant incidence of tumors at sites distant from the site of application. These experiments indicate that connective tissue of rats is not unusually sensitive to tumor induction by these compounds and that subcutaneous injection in the rat is a useful system for the evaluation of potential carcinogens.