Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer:
The present AOP describes the prolonged activation of Cyp2E1 resulting in liver cancer. Cyp2E1 is a cytochrome P450 mono-oxygenase that bioactivates over 85 substrates, thereby creating electrophilic metabolites and oxidative stress. Mono-oxygenation of these substrates to their reactive metabolites...
Gespeichert in:
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| Weitere Verfasser: | , |
| Format: | Elektronisch E-Book |
| Sprache: | English |
| Veröffentlicht: |
Paris
OECD Publishing
2021
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| Schriftenreihe: | OECD Series on Adverse Outcome Pathways
no.19 |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Zusammenfassung: | The present AOP describes the prolonged activation of Cyp2E1 resulting in liver cancer. Cyp2E1 is a cytochrome P450 mono-oxygenase that bioactivates over 85 substrates, thereby creating electrophilic metabolites and oxidative stress. Mono-oxygenation of these substrates to their reactive metabolites, and the accompanying oxidative stress produced during metabolism, pose health risks because they lead to hepatotoxicity and, often, to liver cancer. The MIE occurs when Cyp2E1 binds a substrate. The Cyp2E1 catalytic cycle is prone to decoupling, which produces oxidative stress (KE1), and mono-oxidation of substrates produces reactive metabolites. Both reactive oxygen species and metabolites cause cytotoxicity (KE2). However, following injury, the liver is able to regenerate itself through an increase in cellular proliferation (KE3). Under conditions of chronic activation of Cyp2E1, excessive chronic increases in levels of reactive oxygen species and cell death, and subsequent dysregulated cellular proliferation, leads to tumour formation (AO). |
| Beschreibung: | 1 Online-Ressource (61 p.) |
| DOI: | 10.1787/56e9bbf0-en |
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| 520 | |a The present AOP describes the prolonged activation of Cyp2E1 resulting in liver cancer. Cyp2E1 is a cytochrome P450 mono-oxygenase that bioactivates over 85 substrates, thereby creating electrophilic metabolites and oxidative stress. Mono-oxygenation of these substrates to their reactive metabolites, and the accompanying oxidative stress produced during metabolism, pose health risks because they lead to hepatotoxicity and, often, to liver cancer. The MIE occurs when Cyp2E1 binds a substrate. The Cyp2E1 catalytic cycle is prone to decoupling, which produces oxidative stress (KE1), and mono-oxidation of substrates produces reactive metabolites. Both reactive oxygen species and metabolites cause cytotoxicity (KE2). However, following injury, the liver is able to regenerate itself through an increase in cellular proliferation (KE3). Under conditions of chronic activation of Cyp2E1, excessive chronic increases in levels of reactive oxygen species and cell death, and subsequent dysregulated cellular proliferation, leads to tumour formation (AO). | ||
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| spelling | Webster, Francina VerfasserIn aut Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer Francina, Webster, Iain B., Lambert and Carole L., Yauk Paris OECD Publishing 2021 1 Online-Ressource (61 p.) Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier OECD Series on Adverse Outcome Pathways no.19 The present AOP describes the prolonged activation of Cyp2E1 resulting in liver cancer. Cyp2E1 is a cytochrome P450 mono-oxygenase that bioactivates over 85 substrates, thereby creating electrophilic metabolites and oxidative stress. Mono-oxygenation of these substrates to their reactive metabolites, and the accompanying oxidative stress produced during metabolism, pose health risks because they lead to hepatotoxicity and, often, to liver cancer. The MIE occurs when Cyp2E1 binds a substrate. The Cyp2E1 catalytic cycle is prone to decoupling, which produces oxidative stress (KE1), and mono-oxidation of substrates produces reactive metabolites. Both reactive oxygen species and metabolites cause cytotoxicity (KE2). However, following injury, the liver is able to regenerate itself through an increase in cellular proliferation (KE3). Under conditions of chronic activation of Cyp2E1, excessive chronic increases in levels of reactive oxygen species and cell death, and subsequent dysregulated cellular proliferation, leads to tumour formation (AO). Environment Social Issues/Migration/Health Lambert, Iain B... MitwirkendeR ctb Yauk, Carole L... MitwirkendeR ctb FWS01 ZDB-13-SOC FWS_PDA_SOC https://doi.org/10.1787/56e9bbf0-en Volltext |
| spellingShingle | Webster, Francina Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer Environment Social Issues/Migration/Health |
| title | Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer |
| title_auth | Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer |
| title_exact_search | Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer |
| title_full | Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer Francina, Webster, Iain B., Lambert and Carole L., Yauk |
| title_fullStr | Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer Francina, Webster, Iain B., Lambert and Carole L., Yauk |
| title_full_unstemmed | Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer Francina, Webster, Iain B., Lambert and Carole L., Yauk |
| title_short | Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer |
| title_sort | adverse outcome pathway on cyp2e1 activation leading to liver cancer |
| topic | Environment Social Issues/Migration/Health |
| topic_facet | Environment Social Issues/Migration/Health |
| url | https://doi.org/10.1787/56e9bbf0-en |
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