Comparative genotoxicity studies of ethyl carbamate and related chemicals: further support for vinyl carbamate as a proximate carcinogenic metabolite
- 1 January 1982
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 3 (12), 1437-1441
- https://doi.org/10.1093/carcin/3.12.1437
Abstract
In vivo and/or in vitro mammalian cell systems were used to evaluate sister chromatid exchange (SCE) induction and gene mutagenesis effects following exposure to ethyl carbamate (urethane), vinyl carbamate, ethyl N-hydroxycarbamate, and 2-hydroxyethyl carbamate. Although ethyl carbamate caused dose-dependent increases in SCE when injected into mice, it was ineffective for inducing SCE and gene mutation (6-thioguanine resistance) in Chinese hamster V-79 cells cultured with or without the addition of S9 enzyme mix during treatment. Chemical-specific patterns of genotoxicity were evident for the known or suspect metabolites under test: only vinyl carbamate consistently (in vivo and in vitro) revealed strong activity for the genetic endpoints. SCE induction levels of 5–8 times baseline were observed after animal or cell culture exposures to vinyl carbamate. Doses required to produce this effect in V-79 cells in the presence of S9 mix were ∼100 times lower than those needed when S9 was absent. The extensive gene mutagenesis (approaching 600 mutants/106 survivors) noted was completely dependent upon the presence of S9 mix. These observations are consistent with current theory holding that vinyl carbamate is a metabolic intermediate of ethyl carbamate, and is converted to the ultimately reactive species (presumably, vinyl carbamate epoxide) which is responsible for ethyl carbamate carcinogenesis.This publication has 15 references indexed in Scilit:
- Role of metabolic activation in the sister chromatid exchange-inducing activity of ethyl carbamate (Urethane) and vinyl carbamateMutation Research/Genetic Toxicology, 1981
- IDENTIFICATION OF COCARCINOGENS AND THEIR POTENTIAL MECHANISMS OF ACTION USING C3H10T1/2CL8 MOUSE EMBRYO FIBROBLASTS1981
- RAT BLADDER CELL-MEDIATED MUTAGENESIS OF CHINESE-HAMSTER V79 CELLS AND METABOLISM OF BENZO[A]PYRENE1981
- COMPARATIVE CARCINOGENICITIES AND MUTAGENICITIES OF VINYL CARBAMATE, ETHYL CARBAMATE, AND ETHYL N-HYDROXYCARBAMATE1980
- MUTAGENESIS AND MORPHOLOGICAL TRANSFORMATION OF MAMMALIAN-CELLS BY A NON-BAY-REGION POLYCYCLIC CYCLOPENTA(CD)PYRENE AND ITS 3,4-OXIDE1980
- Urethane and hydroxyurethane induce sister-chromatid exchanges in cultured human lymphocytesMutation Research/Genetic Toxicology, 1979
- The relationship between transformation and somatic mutation in human and Chinese hamster cellsCell, 1978
- VINYL CARBAMATE AS A PROMUTAGEN AND A MORE CARCINOGENIC ANALOG OF ETHYL CARBAMATE1978
- The mutagenic action of urethaneMutation Research/Reviews in Genetic Toxicology, 1976
- Urethan Induced Acceleration of Hexobarbital Metabolism.Experimental Biology and Medicine, 1960