Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocytes were prepared from rainbow trout by perfusion in situ with collagenase and hyaluronidase. Preparations normally showed high initial viability (95 +/- 5% dye exclusion, 92 +/- 5% lactate dehydrogenase retention) and gradually decreased in viability and glutathione concentration over 5 hours. Cellular metabolism of aflatoxin B1 (AFB1), a potent hepatocarcinogen, was characterized by an investigation of the following parameters: kinetics of AFB1 metabolism and DNA adduct formation, dose response, viabilities of detoxication and activation pathways with time, influence of organic solvents, and effect of variation in cell concentration. The AFB1 metabolites and DNA adducts were resolved and quantitated by high-performance liquid chromatography. From these results a standardized assay procedure was derived which we used to examine AFB1 metabolism and DNA adduct formation in hepatocytes from fish fed dietary substances known to alter the carcinogenic response to this mycotoxin. Dietary beta-naphthoflavone, which strongly inhibits AFB1 carcinogenesis in rainbow trout, dramatically and reproducibly altered AFB1 binding and metabolism in isolated hepatocytes. Overall rate of AFB1 metabolism and rates of detoxication reactions increased, whereas DNA binding decreased. Dietary cyclopropenoid fatty acids, powerful synergists and promoters of AFB1 carcinogenesis in trout, also repressed AFB1-DNA binding. Both dietary factors appeared to depress initial DNA damage by AFB1 but operated through different metabolic pathways to do so.
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PMID:Dietary modification of aflatoxin B1 carcinogenesis: mechanism studies with isolated hepatocytes from rainbow trout. 643 Dec 90

A sensitive cell-mediated assay has been developed for testing the mutagensis of liver carcinogens. Mutagenesis was detected in Chinese hamster V79 cells that were cocultivated with hepatocytes isolated after collagenase/hyaluronidase digestion of rat liver slices. Mutations were characterized by resistance to ouabain and 6-thioguanine. Seven of the nitrosamines, which are potent liver carcinogens, exhibited a mutagenic response. Mutagensis with the carcinogens could be detected at micromolar doses. The polyaromatic hydrocarbon benzo(a)pyrene, which is not a liver carcinogen, but can cause fibrosarcomas, was not mutagenic in this assay, but was mutagenic in a fibroblast-mediated assay. The liver carcinogen, aflatoxin B1, which usually does not induce fibrosarcomas, exhibited an inverse situation; it was mutagenic for V79 cells in the presence of liver cells but not in the presence of fibroblasts. We suggest that the use of various cell types, including hepatocytes prepared by the slicing method for carcinogen metabolism, and mutable V79 cells offers a sensitive assay for determining the mutagenic potential of chemical carcinogens, and may also allow a study of their organ specificity.
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PMID:The use of liver cell cultures in mutagenesis studies. 678 35