Cargando…
Differences in Metabolism of Vinylidene Chloride Between Mice and Rats
The present finding that mice metabolize a greater proportion of an oral dose (50 mg/kg) of vinylidence chloride. (1,1 - dichloroethylene, DCE) than rats implies (a) that the efficiency of DCE metabolism follows the known activity of cytochrome P-450 in the organs of these animals, and (b) that, in...
Autores principales: | , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
1978
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2009538/ https://www.ncbi.nlm.nih.gov/pubmed/638019 |
_version_ | 1782136134807060480 |
---|---|
author | Jones, B. K. Hathway, D. E. |
author_facet | Jones, B. K. Hathway, D. E. |
author_sort | Jones, B. K. |
collection | PubMed |
description | The present finding that mice metabolize a greater proportion of an oral dose (50 mg/kg) of vinylidence chloride. (1,1 - dichloroethylene, DCE) than rats implies (a) that the efficiency of DCE metabolism follows the known activity of cytochrome P-450 in the organs of these animals, and (b) that, in accordance with the LD(50) values, the real exposure (expressed as the amount of DCE metabolized) is relatively higher for orally dosed mice than rats, and (c) that DCE carcinogenicity would appear to be more likely in mice than rats. Mice metabolize DCE simiarly to rats (Jones and Hathway, 1977) but there are some differences. Thus, qualitatively, treated mice (but not rats) excrete a small amount of N-acetyl-S-(2carboxymethyl)cysteine. Quantitatively, (i) the relative proportions of the N-acetyl-S-(2-cysteinyl acetyl derivative that are formed in mice and rats parallel the activity of liver glutathione-S-epoxide transferase in these rodents, and (ii) there are marked differences in the proportions of DCE metabolites belonging to the chloroacetic acid branch of the metabolic pathway. Furthermore, the previously assumed β-thionase hydrolysis of thiodiglycollic acid (Jones and Hathway, 1977) is now established in vivo, and the possible biogenesis of the N-acetyl-S-cysteinyl acetyl derivative is verified by another tracer study. The conclusion is drawn that the DCE metabolites, 1,1-dichloroethylene oxide and chloroacetyl chloride, may be important to murine DCE carcinogenicity. |
format | Text |
id | pubmed-2009538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1978 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20095382009-09-10 Differences in Metabolism of Vinylidene Chloride Between Mice and Rats Jones, B. K. Hathway, D. E. Br J Cancer Articles The present finding that mice metabolize a greater proportion of an oral dose (50 mg/kg) of vinylidence chloride. (1,1 - dichloroethylene, DCE) than rats implies (a) that the efficiency of DCE metabolism follows the known activity of cytochrome P-450 in the organs of these animals, and (b) that, in accordance with the LD(50) values, the real exposure (expressed as the amount of DCE metabolized) is relatively higher for orally dosed mice than rats, and (c) that DCE carcinogenicity would appear to be more likely in mice than rats. Mice metabolize DCE simiarly to rats (Jones and Hathway, 1977) but there are some differences. Thus, qualitatively, treated mice (but not rats) excrete a small amount of N-acetyl-S-(2carboxymethyl)cysteine. Quantitatively, (i) the relative proportions of the N-acetyl-S-(2-cysteinyl acetyl derivative that are formed in mice and rats parallel the activity of liver glutathione-S-epoxide transferase in these rodents, and (ii) there are marked differences in the proportions of DCE metabolites belonging to the chloroacetic acid branch of the metabolic pathway. Furthermore, the previously assumed β-thionase hydrolysis of thiodiglycollic acid (Jones and Hathway, 1977) is now established in vivo, and the possible biogenesis of the N-acetyl-S-cysteinyl acetyl derivative is verified by another tracer study. The conclusion is drawn that the DCE metabolites, 1,1-dichloroethylene oxide and chloroacetyl chloride, may be important to murine DCE carcinogenicity. Nature Publishing Group 1978-03 /pmc/articles/PMC2009538/ /pubmed/638019 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Articles Jones, B. K. Hathway, D. E. Differences in Metabolism of Vinylidene Chloride Between Mice and Rats |
title | Differences in Metabolism of Vinylidene Chloride Between Mice and Rats |
title_full | Differences in Metabolism of Vinylidene Chloride Between Mice and Rats |
title_fullStr | Differences in Metabolism of Vinylidene Chloride Between Mice and Rats |
title_full_unstemmed | Differences in Metabolism of Vinylidene Chloride Between Mice and Rats |
title_short | Differences in Metabolism of Vinylidene Chloride Between Mice and Rats |
title_sort | differences in metabolism of vinylidene chloride between mice and rats |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2009538/ https://www.ncbi.nlm.nih.gov/pubmed/638019 |
work_keys_str_mv | AT jonesbk differencesinmetabolismofvinylidenechloridebetweenmiceandrats AT hathwayde differencesinmetabolismofvinylidenechloridebetweenmiceandrats |