From owner-metabolic-reg@net.bio.net Wed Oct 25 22:00:00 1995 Path: biosci!ciit.org!schlosser From: schlosser@ciit.org (Paul M. Schlosser) Newsgroups: bionet.metabolic-reg Subject: Re: Some idle speculation Date: 26 Oct 1995 11:22:46 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 53 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net In article , cam@rschp1.anu.edu.au (Cameron Neylon) wrote: > >In article , schlosser@ciit.org >(Paul M. Schlosser) wrote: > [snip] >> For the liver, freshly isolated >> hepatocytes are then preferred, but there is a fair bit of art/effort to >> getting and using them on a regular basis ... [snip] > >And of course even if you are using a system in which the intracellular >characteristics are very close to what happens in vivo, then you have to >start worrying about the extracellular environment. [snip] There at least, the proof is in the pudding. Metabolism studies from freshly isolated rodent hepatocytes predict quite well the uptake and blood levels of, for example, furan, when other physiological parameters (blood flows, tissue sizes, partition coefficients) are fixed based on independent measurements. For long-term hepatocyte cultures, this is not the case. Most of our experience is with cytochrome P450-mediated metabolism, and it may certainly be the case that other pathways are more significantly effected. For purposes of predicting effects in humans, the best that we can do in most cases is some experiments with donor tissues. ("Excuse me, would you mind breathing furan for 6 hours and allow us to take blood samples along the way?") Our presumption is that, despite the draw-backs, such data is superior to the assumptions one must otherwise make, such as alometric scaling. Paul ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Paul M. Schlosser, Ph.D. Chemical Industry Institute of Toxicology (CIIT) P.O. Box 12137 6 Davis Drive (not needed for regular mail) Research Triangle Park, NC 27709 schlosser@ciit.org _________________________ _____________________________________ _________________________ | | _________________________ | ////// //// //// ////////// | _________________________ | // // // // // // // | _________________________ | // // // // | _________________________ | // // // // | _________________________ | // // // // // | _________________________ | ////// //// //// //// | _________________________ |_____________________________________| .