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Pharmacometabolomic Pathway Response of Effective Anticancer Agents on Different Diets in Rats with Induced Mammary Tumors

1
Division of Systems Biology, National Center for Toxicological Research, Jefferson, AR 72079, USA
2
Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA
3
Department of Surgery, Chemoprevention Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA
*
Author to whom correspondence should be addressed.
Metabolites 2019, 9(7), 149; https://doi.org/10.3390/metabo9070149
Received: 28 May 2019 / Revised: 5 July 2019 / Accepted: 12 July 2019 / Published: 22 July 2019
(This article belongs to the Special Issue Pharmacometabolomics)
Metabolomics is an effective approach to characterize the metabotype which can reflect the influence of genetics, physiological status, and environmental factors such as drug intakes, diet. Diet may change the chemopreventive efficacy of given agents due to the altered physiological status of the subject. Here, metabolomics response to a chemopreventive agent targretin or tamoxifen, in rats with methylnitrosourea-induced tumors on a standard diet (4% fat, CD) or a high fat diet (21% fat, HFD) was evaluated, and found that (1) the metabolome was substantially affected by diet and/or drug treatment; (2) multiple metabolites were identified as potential pharmacodynamic biomarkers related to targretin or tamoxifen regardless of diet and time; and (3) the primary bile acid pathway was significantly affected by targretin treatment in rats on both diets, and the lysolipid pathway was significantly affected by tamoxifen treatment in rats on the high fat diet. View Full-Text
Keywords: pharmacometabolomics; standard diet; high fat diet; protective anticancer agent; targretin; tamoxifen pharmacometabolomics; standard diet; high fat diet; protective anticancer agent; targretin; tamoxifen
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Cao, Z.; Miller, M.S.; Lubet, R.A.; Grubbs, C.J.; Beger, R.D. Pharmacometabolomic Pathway Response of Effective Anticancer Agents on Different Diets in Rats with Induced Mammary Tumors. Metabolites 2019, 9, 149.

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