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We would like to study human intestinal metabolism (intrinsic clearance) of a food contaminant (a cyanotoxin). Apparently this molecule is involved into Phase II metabolism (Gluthatione-S transferase essentially) in liver.
We wanted to use human intestinal microsomes but they lack of Phase II enzymes. What do you think about intestinal S9 fraction in this case ? Do you have other ideas?
Genetic Toxicology of Food Contaminants Unit
Laboratory for Studies and Research on Veterinary Drugs ans Disinfectants
French Food Safety Agency - Fougeres
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The answer to this question is not so easy. Indeed, if the enzyme is only a soluble enzyme, microsomes will not help to measure activity. S9 fraction seemed to be a good alternative because all phase II enzymes are present. However, they are often diluted and thus it is hard to quantify low acitivtities. Moreover, to date, if it is easy to measure an intrinsic clearance on S9 fractions, there is no way to extrapolate it. If MPPGI (microsomal protein per gram of intestine) factors for microsomes could be found in literature, there is a lack of MPPGI factors for S9 fractions. To my mind, I will use intestinal slices instead of S9 fractions because some publications described how to extrapolate intrinsic clearance for liver slice to the organ and I believe that the same protocol could be used for intestinal tissue (van Eijkeren 2000 (RIVM report), de Graaf et al. 2001 (DMD), de Kanter et al. 2004 (Xenobiotica)). To conclude, to study phase II enzymes, I will use S9 fractions for characterization a
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