NMR spectroscopic analyses of liver phosphatidylcholine and phosphatidylethanolamine biosynthesis in rats exposed to peroxisome proliferators-A class of nongenotoxic hepatocarcinogens
Reo, NV; Adinehzadeh, M
HERO ID
1250139
Reference Type
Journal Article
Year
2000
Language
English
PMID
| HERO ID | 1250139 |
|---|---|
| In Press | No |
| Year | 2000 |
| Title | NMR spectroscopic analyses of liver phosphatidylcholine and phosphatidylethanolamine biosynthesis in rats exposed to peroxisome proliferators-A class of nongenotoxic hepatocarcinogens |
| Authors | Reo, NV; Adinehzadeh, M |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 164 |
| Issue | 2 |
| Page Numbers | 113-126 |
| Abstract | Peroxisome proliferators (PPs) are commercial/industrial chemicals that display tumor promoter activity in rodents. The mechanism is not completely understood, and our ability to predict tumorigenicity a priori is even less developed. Wy-14,643, perfluorooctanoic acid (PFOA), and di(2-ethylhexyl)phthalate (DEHP) are strong, moderate, and weak tumor promoters, respectively, while perfluorodecanoic acid (PFDA) lacks promoter activity. This investigation examined the effects of these PPs on the biosyntheses of phosphatidylcholine (PtdC) and phosphatidylethanolamine (PtdE) in rat liver. After exposure to PPs, rats were administered [1-(13)C]choline + [2-(13)C]ethanolamine and liver extracts were analyzed by (31)P and (13)C NMR. The ratio of choline-derived to ethanolamine-derived phospholipids, R(c/e), was significantly affected by all PPs (p < 0. 05). R(c/e) values were in the order Wy-14,643 > PFOA > DEHP > control > PFDA. The amounts of PtdC derived via the CDP-choline pathway versus PtdE-N-methyltransferase (PEMT) activity was 71 vs 29% in controls. This distribution was significantly affected by treatments with Wy-14,643 (95 vs 5%), DEHP (87 vs 13%), and PFDA (39 vs 61%) (p < 0.02). Data suggest that Wy-14,643, PFOA, and DEHP cause a preference for choline and the CDP-choline pathway for biosynthesis of PtdC. Additionally, Wy-14,643 and DEHP inhibited the PEMT pathway. In contrast, PFDA-treated rats showed a preference for ethanolamine, and PtdC was predominately synthesized through the PEMT pathway. These data corroborate studies by Vance and co-workers which suggest that the pathways for PtdC biosynthesis are important for hepatocarcinogenesis. Further studies to evaluate the potential of these measurements as a biomarker for PP-associated tumorigenesis is warranted. |
| Doi | 10.1006/taap.2000.8901 |
| Pmid | 10764624 |
| Wosid | WOS:000086794000001 |
| Url | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0034655357&doi=10.1006%2ftaap.2000.8901&partnerID=40&md5=28fea90439b61ebab1fd434b2f425cb5 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0034655357&doi=10.1006%2ftaap.2000.8901&partnerID=40&md5=28fea90439b61ebab1fd434b2f425cb5 |
| Is Public | Yes |
| Language Text | English |
| Keyword | peroxisome proliferators; liver phospholipids; phosphatidylcholine; phosphatidylethanolamine; NMR spectroscopy |
| Relationship(s) |
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