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S9 fraction

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The S9 fraction is the product of an organ tissue homogenate used in biological assays. The S9 fraction is most frequently used in assays that measure the metabolism of drugs and other xenobiotics. It is defined by the U.S. National Library of Medicine's "IUPAC Glossary of Terms Used in Toxicology"[1] as the "Supernatant fraction obtained from an organ (usually liver) homogenate by centrifuging at 9000 g for 20 minutes in a suitable medium; this fraction contains cytosol and microsomes." The microsomes component of the S9 fraction contain cytochrome P450 isoforms (phase I metabolism) and other enzyme activities. The cytosolic portion contains the major part of the activities of transferases (phase II metabolism).[2] The S9 fraction is easier to prepare than purified microsomes.[3]

Applications

The S9 fraction has been used in conjunction with the Ames test[4] to assess the mutagenic potential of chemical compounds.[5] Chemical substances sometimes require metabolic activation in order to become mutagenic. Furthermore, the metabolic enzymes of bacteria used in the Ames test differ substantially from those in mammals. Therefore, to mimic the metabolism of test substance that would occur in mammals, the S9 fraction is often added to the Ames test.

The S9 fraction has also been used to assess the metabolic stability of candidate drugs.[6]

References

  1. ^ Duffus JH, Nordberg M, Templeton DM (2007). "Glossary of Terms Used in Toxicology, 2nd Edition". Pure Appl Chem. 79 (7): 1153–1344. doi:10.1351/pac200779071153.
  2. ^ Greim, Helmut; Snyder, Robert (2008). Toxicology and risk assessment: a comprehensive introduction. Wiley-Interscience. p. 387. ISBN 0-470-86893-7.
  3. ^ Vogel, H. Gerhard (2006). Drug discovery and evaluation: safety and pharmacokinetic assays. Springer. p. 509. ISBN 3-540-25638-5.
  4. ^ Mortelmans K, Zeiger E (November 2000). "The Ames Salmonella/microsome mutagenicity assay". Mutat. Res. 455 (1–2): 29–60. doi:10.1016/S0027-5107(00)00064-6. PMID 11113466.
  5. ^ Sakura, Atsushi; Suzuki, Satoshi; Satoh, Tetsuo (2004). "Improvement of the Ames test using human liver S9 preparation". In Yan, Zhengyin; Caldwell, Gary (eds.). Optimization in drug discovery: in vitro methods. Methods in pharmacology and toxicology. Humana Press. pp. 325–336. ISBN 1-58829-332-7.
  6. ^ Wu W-N, McKown LA (2004). "Chapter 11: In Vitro Drug Metabolite Profiling Using Hepatic S9 and Human Liver Microsomes". In Yan Z, Cadwell GW (eds.). Optimization in Drug Discovery: In Vitro Methods (Methods in Pharmacology and Toxicology). Totowa, NJ: Humana Press. pp. 163–184. doi:10.1385/1-59259-800-5:163. ISBN 1-58829-332-7.

Further reading

  • Gad, Shayne Cox (2009). "Genotoxicity". Drug Safety Evaluation. Pharmaceutical Development Series (2nd ed.). John Wiley and Sons. pp. 253 et seq. ISBN 978-0-470-25316-8.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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