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Tamoxifen, a widely used antiestrogenic agent for adjuvant therapy against estrogen\u2010positive breast cancer, possesses side effects such as hepatic steatosis and phospholipidosis (PLD). In the present study, we administered tamoxifen to Sprague\u2013Dawley rats and used lipidomics to reveal tamoxifen\u2010induced alteration of the hepatic lipid profile and its association with the plasma lipid profile. Treatment with tamoxifen for 28\u2009days caused hepatic PLD in rats. We compared the plasma and liver lipid profiles in treated vs. untreated rats using a multivariate analysis to determine differences between the two groups. In total, 25 plasma and 45 liver lipids were identified and altered in the tamoxifen\u2010treated group. Of these lipids, arachidonic acid (AA)\u2010containing phosphatidylcholines (PCs), such as PC (17:0\/20:4) and PC (18:1\/20:4), were commonly reduced in both plasma and liver. Conversely, tamoxifen increased other phosphoglycerolipids in the liver, such as phosphatidylethanolamine (18:1\/18:1) and phosphatidylinositol (18:0\/18:2). We also examined alteration of AA\u2010containing PCs and some phosphoglycerolipids in the pre\u2010PLD stage and found that these lipid alterations were initiated before pathological alteration in the liver. In addition, changes in plasma and liver levels of AA\u2010containing PCs were linearly associated. Moreover, levels of free AA and mRNA levels of AA\u2010synthesizing enzymes, such as fatty acid desaturase 1 and 2, were decreased by tamoxifen treatment. Therefore, our study demonstrated that AA\u2010containing PCs might have potential utility as novel and predictive biomarkers for tamoxifen\u2010induced PLD. Copyright \u00a9 2017 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3442","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T03:31:15Z","timestamp":1485833475000},"page":"943-953","source":"Crossref","is-referenced-by-count":18,"title":["Arachidonic acid\u2010containing phosphatidylcholine characterized by consolidated plasma and liver lipidomics as an early onset marker for tamoxifen\u2010induced hepatic phospholipidosis"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1035-3454","authenticated-orcid":false,"given":"Kosuke","family":"Saito","sequence":"first","affiliation":[{"name":"Division of Medicinal Safety Science National Institute of Health Sciences  Setagaya Tokyo 158\u20108501 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Goda","sequence":"additional","affiliation":[{"name":"Toxicology Research Lab Central Pharmaceutical Research Institute, Japan Tobacco Inc.  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