Activation of [14C] chlorobiphenyls to protein-binding metabolites by rat liver microsomes
| Autor: | Sigrun Hesse, Thomas Wolff, Margot Mezger |
|---|---|
| Rok vydání: | 1978 |
| Předmět: |
Male
Antimetabolites Glucuronidation Epoxide In Vitro Techniques Toxicology chemistry.chemical_compound Biotransformation Styrene oxide Albumins medicine Animals TCPO Secondary metabolism Superoxide General Medicine Polychlorinated Biphenyls Rats Kinetics chemistry Biochemistry Microsomes Liver Phenobarbital Oxidation-Reduction medicine.drug Protein Binding |
| Zdroj: | Chemico-biological interactions. 20(3) |
| ISSN: | 0009-2797 |
| Popis: | The irreversible binding of [14C] 2,2'-di- and [14C] 2,4,5,2',4',5'-hexachlorobiphenyl ([14C] DCB and [14C] HCB) to protein was studied in the presence of rat liver microsomes and a NADPH-generating system. Protein-bound radioactivity was found with [14C] DCB but not with [14C] HCB. The binding of 14C-metabolites was increased by pretreatment of the rats with phenobarbital or polychlorinated biphenyls. Protein binding was linear for 80 min. In contrast, monohydroxy-metabolites of DCB were formed and degraded within 40 min. Inhibition of secondary oxidation of DCB by scavenging superoxide anions or by glucuronidation of the monophenols markedly decreased the protein binding. Addition of trichloropropene oxide or styrene oxide, both inhibitors of epoxide hydrase, did not significantly stimulate the binding. The results suggest that the majority of reactive metabolites of DCB arise from secondary metabolism, i.e., the subsequent oxidation of the phenolic metabolites. Arene oxides, the primary products, appear to play a minor role in the protein binding of DCB. |
| Databáze: | OpenAIRE |
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