Gamma-ray Irradiation of Rodent Diets Alters the Urinary Metabolome in Rats with Chemically Induced Mammary Cancer
In this study, a comparative, untargeted metabolomics approach was applied to compare urinary metabolite profiles of rats fed irradiated and non-irradiated diets. γ-Irradiated and non-irradiated NIH 7001 diet was given orally to animals beginning 5 days after exposure to the carcinogen N-methyl-N-ni...
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MDPI AG
2022-10-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/10/976 |
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| author | Jeevan K. Prasain Landon S. Wilson Clinton Grubbs Stephen Barnes |
| author_facet | Jeevan K. Prasain Landon S. Wilson Clinton Grubbs Stephen Barnes |
| author_sort | Jeevan K. Prasain |
| collection | DOAJ |
| description | In this study, a comparative, untargeted metabolomics approach was applied to compare urinary metabolite profiles of rats fed irradiated and non-irradiated diets. γ-Irradiated and non-irradiated NIH 7001 diet was given orally to animals beginning 5 days after exposure to the carcinogen N-methyl-N-nitrosourea and continued for 120 days. There was a 36% reduction in mammary tumor incidence in rats consuming the γ-irradiated diet, compared to rats receiving the non-irradiated form of the same diet. Urine samples from rats fed with γ-irradiated and non-irradiated diets were analyzed using nanoLC-MS/MS on a Q-TOF mass spectrometer, collecting positive and negative ion data. Data processing involved feature detection and alignment with MS-DIAL, normalization, mean-centering and Pareto scaling, and univariate and multivariate statistical analysis using MetaboAnalyst, and pathway analysis with Mummichog. Unsupervised Principal Component Analysis and supervised Partial Least Squares-Discriminant Analysis of both negative and positive ions revealed separation of the two groups. The top 25 metabolites from variable importance in projection scores >1 showed their contributions in discriminating urines the γ-irradiated diet fed group from non-irradiated control diet group. Consumption of the γ-irradiated diet led to alteration of several gut microbial metabolites such as phenylacetylglycine, indoxyl sulfate, kynurenic acid, hippurate and betaine in the urine. This study provides insights into metabolic changes in rat urine in response to a γ-irradiated diet which may be associated with mammary cancer prevention. |
| first_indexed | 2024-03-09T19:49:11Z |
| format | Article |
| id | doaj.art-60448f5a54614a77a082f42ad48821b2 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T19:49:11Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-60448f5a54614a77a082f42ad48821b22023-11-24T01:16:13ZengMDPI AGMetabolites2218-19892022-10-01121097610.3390/metabo12100976Gamma-ray Irradiation of Rodent Diets Alters the Urinary Metabolome in Rats with Chemically Induced Mammary CancerJeevan K. Prasain0Landon S. Wilson1Clinton Grubbs2Stephen Barnes3Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USATargeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USAIn this study, a comparative, untargeted metabolomics approach was applied to compare urinary metabolite profiles of rats fed irradiated and non-irradiated diets. γ-Irradiated and non-irradiated NIH 7001 diet was given orally to animals beginning 5 days after exposure to the carcinogen N-methyl-N-nitrosourea and continued for 120 days. There was a 36% reduction in mammary tumor incidence in rats consuming the γ-irradiated diet, compared to rats receiving the non-irradiated form of the same diet. Urine samples from rats fed with γ-irradiated and non-irradiated diets were analyzed using nanoLC-MS/MS on a Q-TOF mass spectrometer, collecting positive and negative ion data. Data processing involved feature detection and alignment with MS-DIAL, normalization, mean-centering and Pareto scaling, and univariate and multivariate statistical analysis using MetaboAnalyst, and pathway analysis with Mummichog. Unsupervised Principal Component Analysis and supervised Partial Least Squares-Discriminant Analysis of both negative and positive ions revealed separation of the two groups. The top 25 metabolites from variable importance in projection scores >1 showed their contributions in discriminating urines the γ-irradiated diet fed group from non-irradiated control diet group. Consumption of the γ-irradiated diet led to alteration of several gut microbial metabolites such as phenylacetylglycine, indoxyl sulfate, kynurenic acid, hippurate and betaine in the urine. This study provides insights into metabolic changes in rat urine in response to a γ-irradiated diet which may be associated with mammary cancer prevention.https://www.mdpi.com/2218-1989/12/10/976irradiated dietmetabolomicschemopreventionMNUbreast cancer |
| spellingShingle | Jeevan K. Prasain Landon S. Wilson Clinton Grubbs Stephen Barnes Gamma-ray Irradiation of Rodent Diets Alters the Urinary Metabolome in Rats with Chemically Induced Mammary Cancer Metabolites irradiated diet metabolomics chemoprevention MNU breast cancer |
| title | Gamma-ray Irradiation of Rodent Diets Alters the Urinary Metabolome in Rats with Chemically Induced Mammary Cancer |
| title_full | Gamma-ray Irradiation of Rodent Diets Alters the Urinary Metabolome in Rats with Chemically Induced Mammary Cancer |
| title_fullStr | Gamma-ray Irradiation of Rodent Diets Alters the Urinary Metabolome in Rats with Chemically Induced Mammary Cancer |
| title_full_unstemmed | Gamma-ray Irradiation of Rodent Diets Alters the Urinary Metabolome in Rats with Chemically Induced Mammary Cancer |
| title_short | Gamma-ray Irradiation of Rodent Diets Alters the Urinary Metabolome in Rats with Chemically Induced Mammary Cancer |
| title_sort | gamma ray irradiation of rodent diets alters the urinary metabolome in rats with chemically induced mammary cancer |
| topic | irradiated diet metabolomics chemoprevention MNU breast cancer |
| url | https://www.mdpi.com/2218-1989/12/10/976 |
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