Comparative Xenobiotic Metabolism between Tg.AC and p53+/– Genetically Altered Mice and Their Respective Wild Types.
Saved in:
| Title: | Comparative Xenobiotic Metabolism between Tg.AC and p53+/– Genetically Altered Mice and Their Respective Wild Types. |
|---|---|
| Authors: | Sanders, J. M.1 sandersm@niehs.nih.gov, Burka, L. T.1, Chanas, B.1, Matthews, H. B.1 |
| Source: | Toxicological Sciences. May2001, Vol. 61 Issue 1, p54-61. 8p. 1 Chart, 8 Graphs. |
| Subjects: | Transgenic animals, Carcinogens, Genomes, Metabolism, Xenobiotics, Metabolites |
| Abstract: | The use of transgenic animals, such as v-Ha-ras activated (Tg.AC) and p53+/– mice, offers great promise for a rapid and more sensitive assay for chemical carcinogenicity. Some carcinogens are metabolically activated; therefore, it is critical that the altered genome of either of these model systems does not compromise their capability and capacity for metabolism of xenobiotics. The present work tests the generally held assumption that xenobiotic metabolism in the Tg.AC and p53+/– mouse is not inherently different from that of the respective wild type, the FVB/N and C57BL/6 mouse, by comparing each genotype's ability to metabolize benzene, ethoxyquin, or methacrylonitrile. Use of these representative substrates offers the opportunity to examine arene oxide formation, aromatic ring opening, hydroxylation, epoxidation, O-deethylation, and a number of conjugation reactions. Mice were treated by gavage with 14C-labeled parent compound, excreta were collected, and elimination routes and rates, as well as 14C-derived metabolite profiles in urine, were compared between relevant treatment groups. Results of this study indicated that metabolism of the 3 parent compounds was not appreciably altered between either FVB/N and Tg.AC mice or C57BL/6 and p53+/– mice. Further, expression of CYP1A2, CYP2E1, CYP3A, and GST-α in liver of naive genetically altered mice was similar to that of corresponding wild-type mice. Thus, these results suggest that the inherent ability of Tg.AC and p53+/– mice to metabolize xenobiotics is not compromised by their altered genomes and would not be a factor in data interpretation of toxicity studies using either transgenic mouse line. [ABSTRACT FROM PUBLISHER] |
| Copyright of Toxicological Sciences is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
|---|---|
| Header | DbId: egs DbLabel: Engineering Source An: 44406142 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Comparative Xenobiotic Metabolism between Tg.AC and p53+/– Genetically Altered Mice and Their Respective Wild Types. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Sanders%2C+J%2E+M%2E%22">Sanders, J. M.</searchLink><relatesTo>1</relatesTo><i> sandersm@niehs.nih.gov</i><br /><searchLink fieldCode="AR" term="%22Burka%2C+L%2E+T%2E%22">Burka, L. T.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Chanas%2C+B%2E%22">Chanas, B.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Matthews%2C+H%2E+B%2E%22">Matthews, H. B.</searchLink><relatesTo>1</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Toxicological+Sciences%22">Toxicological Sciences</searchLink>. May2001, Vol. 61 Issue 1, p54-61. 8p. 1 Chart, 8 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Transgenic+animals%22">Transgenic animals</searchLink><br /><searchLink fieldCode="DE" term="%22Carcinogens%22">Carcinogens</searchLink><br /><searchLink fieldCode="DE" term="%22Genomes%22">Genomes</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolism%22">Metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Xenobiotics%22">Xenobiotics</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolites%22">Metabolites</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The use of transgenic animals, such as v-Ha-ras activated (Tg.AC) and p53+/– mice, offers great promise for a rapid and more sensitive assay for chemical carcinogenicity. Some carcinogens are metabolically activated; therefore, it is critical that the altered genome of either of these model systems does not compromise their capability and capacity for metabolism of xenobiotics. The present work tests the generally held assumption that xenobiotic metabolism in the Tg.AC and p53+/– mouse is not inherently different from that of the respective wild type, the FVB/N and C57BL/6 mouse, by comparing each genotype's ability to metabolize benzene, ethoxyquin, or methacrylonitrile. Use of these representative substrates offers the opportunity to examine arene oxide formation, aromatic ring opening, hydroxylation, epoxidation, O-deethylation, and a number of conjugation reactions. Mice were treated by gavage with 14C-labeled parent compound, excreta were collected, and elimination routes and rates, as well as 14C-derived metabolite profiles in urine, were compared between relevant treatment groups. Results of this study indicated that metabolism of the 3 parent compounds was not appreciably altered between either FVB/N and Tg.AC mice or C57BL/6 and p53+/– mice. Further, expression of CYP1A2, CYP2E1, CYP3A, and GST-α in liver of naive genetically altered mice was similar to that of corresponding wild-type mice. Thus, these results suggest that the inherent ability of Tg.AC and p53+/– mice to metabolize xenobiotics is not compromised by their altered genomes and would not be a factor in data interpretation of toxicity studies using either transgenic mouse line. [ABSTRACT FROM PUBLISHER] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Toxicological Sciences is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=44406142 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1093/toxsci/61.1.54 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 8 StartPage: 54 Subjects: – SubjectFull: Transgenic animals Type: general – SubjectFull: Carcinogens Type: general – SubjectFull: Genomes Type: general – SubjectFull: Metabolism Type: general – SubjectFull: Xenobiotics Type: general – SubjectFull: Metabolites Type: general Titles: – TitleFull: Comparative Xenobiotic Metabolism between Tg.AC and p53+/– Genetically Altered Mice and Their Respective Wild Types. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Sanders, J. M. – PersonEntity: Name: NameFull: Burka, L. T. – PersonEntity: Name: NameFull: Chanas, B. – PersonEntity: Name: NameFull: Matthews, H. B. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 05 Text: May2001 Type: published Y: 2001 Identifiers: – Type: issn-print Value: 10966080 Numbering: – Type: volume Value: 61 – Type: issue Value: 1 Titles: – TitleFull: Toxicological Sciences Type: main |
| ResultId | 1 |
