Abstract
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.
Highlights
The rat model of dimethylbenzanthracene or methylnitrosourea (MNU) induced breast cancer has been employed in the development of new chemopreventive agents, which is highly responsive to a number of regimens that are both hormone related (selective estrogen receptor modulators (SERM), aromatase inhibitors, ovariectomy) [1,2,3] and non-hormone related [4,5]
43, Sprague-Dawley rats were started on Ctrl. Diets: standard diet (CD) or high fat diet (HFD) diet
Our cancer in rats, where the resulted in increased tumor multiplicity and tumor weight and cancer in rats, where the HFD resulted in increased tumor multiplicity and tumor weight and decreased decreased tumor latencyto compared to CD
Summary
The rat model of dimethylbenzanthracene or methylnitrosourea (MNU) induced breast cancer has been employed in the development of new chemopreventive agents, which is highly responsive to a number of regimens that are both hormone related (selective estrogen receptor modulators (SERM), aromatase inhibitors, ovariectomy) [1,2,3] and non-hormone related (agonists for the retinoid X receptor) [4,5]. Our study found that metformin was completely ineffective in the rat MNU model [7]. Diet has been found to affect chemical induced cancer in rats [8,9]. These MNU rat model studies have been performed with rats on a standard diet with a relatively low level of fat using soy as a protein source. The standard human diet in the United State has high levels of fat
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
