Separation and Biochemical Characterization of Rat Liver Parenchymal Cell Subpopulations
Parenchymal cells within the hepatic lobules of the rat are morphologically and biochemically heterogeneous (Shank et al., 1959; Novikoff, 1959; Loud, 1968; Jungermann and Katz, 1982). It has been previously shown that the concentration of cytochrome P-450 and the activities of most cytochrome P-450-dependent monooxygenases are relatively higher in the centrilobular regions than in the periportal regions of the rat liver (Baron et al., 1978; Gooding et al., 1978; Baron and Kawabata, 1983); further, these studies revealed that pretreatment of the animals with phenobarbital intensified this gradation across the liver lobule, whereas after administration of 3-methylcholanthrene the concentration of cytochrome P-450 and the monooxygenase activities were more uniformly distributed. Since very reactive and toxic metabolites are often formed during cytochrome P-450-catalyzed monooxygenations of hepatotoxins, the intralobular distribution of different cytochromes P-450 may be a crucial factor in determining the location of the damage within the hepatic lobules after exposure to several hepatotoxic compounds.
KeywordsParenchymal Cell Hepatic Lobule Liver Parenchymal Cell Centrifugal Elutriation Periportal Region
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- Baron, J., and Kawabata, T., 1983, Intratissue distribution of activating and detoxicating enzymes, in: “Biological Basis of Detoxication”, J. Caldwell and W.B. Jakoby, eds., Academic Press, New York.Google Scholar
- Bernaert, D., Wanson, J.-C, Mosselmans, R., De Parmentier, R., and Drochmans, P., 1979, Separation of adult rat hepatocytes into distinct subpopulations by centrifugal elutriation. Morphological, morphometrical and biochemical characterization of cell fractions, Biol. Cellulaire, 34: 159.Google Scholar
- Glatt, H.R., Billings, R., Platt, K.L., and Oesch, F., 1981, Improvement of the correlation of bacterial mutagenicity with carcinogenicity of benzo (a) pyrene and four of its major metabolites by activation with intact liver cells instead of cell homogenate, Cancer Res., 41: 270.PubMedGoogle Scholar
- Klinger, W., Devereux, T., Fouts, J., Lohr, S., Crawford, D., Diliberto, J., and Sparks, R., 1985, Separation of immature and adult rat hepatocytes into distinct subpopulations by centrifugal elutriation, Arch. Toxicol., Suppl. 8: 469.Google Scholar
- Tonda, K., Hasegawa, T., and Hirata, M., 1983, Effects of phenobarbital and 3-methylcholanthrene pretreatments on monooxygenase activities and proportions of isolated rat hepatocyte subpopulations, Molec Pharmacol., 23: 235.Google Scholar
- Wolf, C.R., Moll, E., Friedberg, T., Oesch, F., Buchmann, A., Kuhlmann, W.D., and Kunz, H.W., 1984, Characterization, localization and regulation of a novel phenobarbital-inducible form of cytochrome P-450 reductase, glutathione transferases and microsomal epoxide hydrolase, Carcinogenesis, 5: 993.PubMedCrossRefGoogle Scholar