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Covalent binding of haloethylenes
Advances in Experimental Medicine and Biology
|January 1, 1981
Summary
Halogenated ethylenes form reactive metabolites that bind to cellular targets like DNA and proteins. These metabolic effects, including increased acetone exhalation, may indicate reactive intermediate formation in vivo.
Area of Science:
- Toxicology
- Biochemistry
- Environmental Health
Background:
- Halogenated ethylenes are industrial chemicals with known toxicities.
- Metabolism of these compounds can generate reactive intermediates.
- Cellular targets for these intermediates include DNA, RNA, proteins, and coenzymes.
Purpose of the Study:
- To investigate the cellular targets and metabolic consequences of halogenated ethylene exposure.
- To identify potential biomarkers for reactive metabolite formation in vivo.
Main Methods:
- Review of existing literature on halogenated ethylene metabolism and toxicity.
- Analysis of proposed binding sites on DNA, RNA, and proteins.
- Consideration of coenzyme alkylation and its metabolic implications.
Main Results:
- Halogenated ethylene metabolites covalently bind to DNA, forming etheno-DNA adducts (e.g., with deoxyguanosine).
- Metabolites also react with RNA, forming etheno-RNA adducts (e.g., 1,N6-ethenoadenosine, 3,N4-ethenocytidine).
- Protein alkylation occurs, particularly at sulfhydryl groups, and coenzymes like coenzyme A can be alkylated, potentially leading to increased acetone exhalation.
Conclusions:
- Halogenated ethylenes generate reactive metabolites that alkylate critical cellular macromolecules.
- The observed metabolic alterations, such as altered coenzyme A function, may serve as indicators of in vivo reactive metabolite formation.
- Further investigation into these metabolic effects is warranted to understand the full toxicological profile.