Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytochrome P-450 3A gene family comprises the dominant forms of cytochrome P-450 found in human liver. We examined as a possible useful system for studying the regulation of cytochrome P-450 3A under controlled conditions in vitro, primary monolayer cultures of human hepatocytes and compared the results with those obtained from the study of cytochrome P-450 3A in the human hepatoblastoma cell line HepG2 or in the human hepatocellular carcinoma cell line TONG/HCC. Using 3A antibodies, 3A cDNAs and 3A3, 3A4, 3A5 and 3A7 isozyme-specific oligonucleotides as probes, we determined that primary human hepatocyte cultures routinely expressed a 3A3/4* immunoreactive protein and 3A mRNA. These gene products were well maintained for many days and were induced by treatment of the cultures with dexamethasone, phenobarbital, macrolide antibiotics, the HMG CoA reductase inhibitor lovastatin or an antifungal agent, clotrimazole. Of six donor livers examined, only two contained mRNA or protein for 3A5, a form found in only a few adult human subjects. In cultures prepared from one of these two livers, 3A5 mRNA was detectable for several days. In cultures of hepatocytes from the remaining four human livers that did not contain 3A5 mRNA or protein, we detected neither spontaneous nor inducible 3A5 proteins or mRNAs. HepG2 cells contained only 3A7 protein, a form found in human fetal liver, even after treatment with inducers. treatment of HepG2 cells with dexamethasone, macrolide antibiotics, phenobarbital and phenobarbital-like inducers or lovastatin produced dose-dependent induction of 3A7 mRNA and 3A7 immunoreactive protein. TONG/HCC cells contained 3A3, 3A4 and 3A5 mRNAs, but only 3A5 immunoreactive protein could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of human liver cytochromes P-450 in family 3A in primary and continuous culture of human hepatocytes. 822 33

Reduced glucose-6-phosphatase, increased GGT activity and reduction of cytochrome P-450 content are considered to be markers of chemical hepatocarcinogenesis in rats. The significance of these changes were studied in certain human liver lesions; adenoma, focal nodular hyperplasia and hepatocellular carcinoma all developed in non-cirrhotic livers. Enzymes showed normal values in 4 out of 5 adenomas, in 2/13 FNH and in 4/18 HCC samples. The decreased cP-450 content in HCC proved to be the most consistent alteration (12/18). Only 3 HCC samples possessed changes off all enzymes. These data suggest that at least those enzymes which are used as markers in rat chemical hepatocarcinogenesis have little or no biological significance in human liver tumors, primarily due to the intertumoral heterogeneity of enzyme activity. Such heterogeneity was observed in the peritumoral "normal" liver tissue, too.
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PMID:Marker Enzymes of Rat Chemical Hepatocarcinogenesis in Human Liver Tumors. 1117 85