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Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs.
The present paper describes a marked induction of liver microsomal cytochrome P-450 and cytosolic DT-diaphorase to cause possible disorder of steroid homeostasis and promotion of carcinogenicity of 4-nitroquinoline N-oxide (4-NQO) in rats by pretreatment with 3,4,5,3',4'-pentachlorobipheny...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
1985
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1568086/ https://www.ncbi.nlm.nih.gov/pubmed/3921354 |
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author | Yoshimura, H Yoshihara, S Koga, N Nagata, K Wada, I Kuroki, J Hokama, Y |
author_facet | Yoshimura, H Yoshihara, S Koga, N Nagata, K Wada, I Kuroki, J Hokama, Y |
author_sort | Yoshimura, H |
collection | PubMed |
description | The present paper describes a marked induction of liver microsomal cytochrome P-450 and cytosolic DT-diaphorase to cause possible disorder of steroid homeostasis and promotion of carcinogenicity of 4-nitroquinoline N-oxide (4-NQO) in rats by pretreatment with 3,4,5,3',4'-pentachlorobiphenyl (PenCB) or 2,3,4,7,8-pentachlorodibenzofuran (PenCDF). The animals were sacrificed 5 days after the pretreatment. These induction experiments showed that 7 alpha-hydroxylation of both progesterone and testosterone in liver microsomes was selectively increased to a great extent, but hydroxylations at the 2 alpha-, 6 beta- and 16 alpha-positions were depressed, together with 5 alpha-reduction. From the same microsomes, three of the strongly induced P-450 isozymes, i.e., high- and low-spin P-448s and P-452, were purified. The last isozyme was most responsible for 7 alpha-hydroxylation of testosterone. The pretreatment, also increased activity of DT-diaphorase and reduction of 4-NQO about 10-fold in liver 9000g supernatants. This reduction of 4-NQO was solely catalyzed by DT-diaphorase and the only product was 4-hydroxylaminoquinoline N-oxide, a proximate carcinogen, indicating that the pretreatment strongly increased production of a proximate carcinogen from 4-NQO. Such an enhancement of the metabolic activation of 4-NQO by the pretreatment was also observed to some extent in the lung and the skin. Persistency of PenCB and PenCDF in the liver of rats was also discussed. |
format | Text |
id | pubmed-1568086 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1985 |
record_format | MEDLINE/PubMed |
spelling | pubmed-15680862006-09-18 Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. Yoshimura, H Yoshihara, S Koga, N Nagata, K Wada, I Kuroki, J Hokama, Y Environ Health Perspect Research Article The present paper describes a marked induction of liver microsomal cytochrome P-450 and cytosolic DT-diaphorase to cause possible disorder of steroid homeostasis and promotion of carcinogenicity of 4-nitroquinoline N-oxide (4-NQO) in rats by pretreatment with 3,4,5,3',4'-pentachlorobiphenyl (PenCB) or 2,3,4,7,8-pentachlorodibenzofuran (PenCDF). The animals were sacrificed 5 days after the pretreatment. These induction experiments showed that 7 alpha-hydroxylation of both progesterone and testosterone in liver microsomes was selectively increased to a great extent, but hydroxylations at the 2 alpha-, 6 beta- and 16 alpha-positions were depressed, together with 5 alpha-reduction. From the same microsomes, three of the strongly induced P-450 isozymes, i.e., high- and low-spin P-448s and P-452, were purified. The last isozyme was most responsible for 7 alpha-hydroxylation of testosterone. The pretreatment, also increased activity of DT-diaphorase and reduction of 4-NQO about 10-fold in liver 9000g supernatants. This reduction of 4-NQO was solely catalyzed by DT-diaphorase and the only product was 4-hydroxylaminoquinoline N-oxide, a proximate carcinogen, indicating that the pretreatment strongly increased production of a proximate carcinogen from 4-NQO. Such an enhancement of the metabolic activation of 4-NQO by the pretreatment was also observed to some extent in the lung and the skin. Persistency of PenCB and PenCDF in the liver of rats was also discussed. 1985-02 /pmc/articles/PMC1568086/ /pubmed/3921354 Text en |
spellingShingle | Research Article Yoshimura, H Yoshihara, S Koga, N Nagata, K Wada, I Kuroki, J Hokama, Y Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. |
title | Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. |
title_full | Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. |
title_fullStr | Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. |
title_full_unstemmed | Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. |
title_short | Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. |
title_sort | inductive effect on hepatic enzymes and toxicity of congeners of pcbs and pcdfs. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1568086/ https://www.ncbi.nlm.nih.gov/pubmed/3921354 |
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