دورية أكاديمية
Assessment of the mode of action of perchloroethylene-induced mouse liver tumors.
| العنوان: | Assessment of the mode of action of perchloroethylene-induced mouse liver tumors. |
|---|---|
| المؤلفون: | Klaunig JE; School of Public Health, Indiana University, Bloomington, IN, USA., Bevan C; Halogenated Solvents Industry Alliance, Inc., Arlington, VA, USA., Gollapudi B; Autumn Ridge Circle N, Midland, MI, USA. |
| المصدر: | Toxicology and industrial health [Toxicol Ind Health] 2024 May; Vol. 40 (5), pp. 272-291. Date of Electronic Publication: 2024 Mar 25. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: SAGE Publications Country of Publication: England NLM ID: 8602702 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-0393 (Electronic) Linking ISSN: 07482337 NLM ISO Abbreviation: Toxicol Ind Health Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : SAGE Publications Original Publication: Princeton, N.J. : Princeton Scientific Pub. Co. |
| مواضيع طبية MeSH: | Tetrachloroethylene*/toxicity , Tetrachloroethylene*/metabolism , Liver Neoplasms*/chemically induced, Mice ; Humans ; Animals ; PPAR alpha/genetics ; PPAR alpha/metabolism ; PPAR alpha/pharmacology ; Liver ; Oxidation-Reduction ; Risk Assessment |
| مستخلص: | Perchloroethylene (PCE) is used as a solvent and chemical intermediate. Following chronic inhalation exposure, PCE selectively induced liver tumors in mice. Understanding the mode of action (MOA) for PCE carcinogenesis in mice is important in defining its possible human cancer risk. The proposed MOA is based on the extensive examination of the peer-reviewed studies that have assessed the mouse liver effects of PCE and its major oxidative metabolite trichloroacetic acid (TCA). Similar to PCE, TCA has also been demonstrated to liver tumors selectively in mice following chronic exposure. The Key Events (KE) of the proposed PCE MOA involve oxidative metabolism of PCE to TCA [KE 1]; activation of the peroxisome proliferator-activated receptor alpha (PPARα) [KE 2]; alteration in hepatic gene expression including cell growth pathways [KE 3]; increase in cell proliferation [KE 4]; selective clonal expansion of hepatic preneoplastic foci [KE 5]; and formation of hepatic neoplasms [KE 6]. The scientific evidence supporting the PPARα MOA for PCE is strong and satisfies the requirements for a MOA analysis. The PPARα liver tumor MOA in rodents has been demonstrated not to occur in humans; thus, human liver cancer risk to PCE is not likely. Competing Interests: Declaration of competing interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Bevan is the Science Director of HSIA, a trade association that represents producers and users of PCE. |
| فهرسة مساهمة: | Keywords: carcinogenesis; mechanism of action; mode of action; mouse liver tumors; perchloroethylene; trichloracetic acid |
| المشرفين على المادة: | TJ904HH8SN (Tetrachloroethylene) 0 (PPAR alpha) |
| تواريخ الأحداث: | Date Created: 20240325 Date Completed: 20240405 Latest Revision: 20240405 |
| رمز التحديث: | 20240405 |
| DOI: | 10.1177/07482337241240188 |
| PMID: | 38523547 |
| قاعدة البيانات: | MEDLINE |
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