Potency of some carbamates as multiple tissue sister chromatid exchange inducers and comparison with known carcinogenic activities

Abstract

The ethyl, ethyl N-hydroxy, isopropyl, and methyl esters of carbamic acid were examined for their abilities to induce sister chromatid exchanges (SCEs) in alveolar macrophages, bone marrow, and regenerating liver cells of C57BL/6J X DBA/2J F1 mice. The relative potencies in inducing SCE, ethyl greater than ethyl N-hydroxy- greater than isopropyl, paralleled previously described activities for induction of lung adenomas in strain A mice. The noncarcinogenic methyl carbamate was inactive in the SCE assay. Relative to bone marrow, regenerating liver and alveolar macrophage cells demonstrated increased susceptibility to carbamate-induced SCE. Of all carbamates studied, only the directly active compound, ethyl N-hydroxycarbamate, produced distinctly different responses in extrahepatic tissues of hepatectomized and intact mice. In intact mice, SCE levels induced by ethyl carbamate in bone marrow and alveolar macrophage cells were not significantly different whether assay followed the last of 12 (three times weekly) serial injections of 2.2 mmol/kg each or after a single injection of 2.2 mmol/kg. Linear regression relationships of log ethyl carbamate versus log SCE or log adenoma response were found to be parallel with the two assays having similar sensitivities.