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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-6-7
pubmed:abstractText
This is an extensive study in a defined initiation-promotion hepatocellular carcinoma model of hepatocarcinogenesis (in rats) in which many important marker enzymes and isoenzymes and 8-hydroxydeoxyguanosine formation have been studied together with two very important cellular proliferating genes, insulin-like growth factor II and c-raf.1, known for their role in hepatocellular cancer development. Experiments were carried out on hepatic tissues of male Sprague-Dawley rats. Variations in different enzyme/isoenzyme activities/contents/expression pattern and 8-hydroxydeoxyguanosine-positive cells were studied. Insulin-like growth factor II and c-raf.1 gene expressions were monitored. A direct shift with increase in size and numbers of lesions was found to occur in different experimental groups. In this study, glutathione peroxidase (1.14 and 1.46-fold) and reduced triphosphopyridine nucleotide (TPNH)-cytochrome-c-reductase (1.94 and 2.94-fold) activities, cytochrome b5 (1.57 and 3.28-fold) and P-450 contents (1.45 and 1.22-fold), glutathione content (1.27 and 1.45-fold) and superoxide dismutase and catalase (1.16 and 1.39-fold) activities in group A animals were found to be lower than those in initiation and promotion studies, respectively. 8-Hydroxydeoxyguanosine-positive nuclei count showed that oxidative damage of nuclear DNA enhanced with the progress of the disease. The insulin-like growth factor II expression was found to be predominant in hepatocellular carcinoma and in early preneoplastic lesions. Unlike insulin-like growth factor II, c-raf.1 expression was located in the late basophilic lesions associated with hepatocellular carcinoma. During the various stages of the development of hepatocellular carcinoma, the enzymes played a significant role in metabolizing carcinogens and thereby scavenging various toxic metabolites or free radicals produced. A sequence of cellular changes starting from the appearance of glycogen storage foci to basophilic foci leading to hepatocellular carcinoma via mixed cell foci varied the activity/content or expression pattern of the enzymes and isoenzymes and in 8-hydroxydeoxyguanosine formation. It has been established that c-raf.1-induced signaling pathways activated by insulin-like growth factor II is implicated in the late stage of development of cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0959-8278
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
363-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17554210-Animals, pubmed-meshheading:17554210-Antioxidants, pubmed-meshheading:17554210-Carcinoma, Hepatocellular, pubmed-meshheading:17554210-Cell Nucleus, pubmed-meshheading:17554210-Deoxyguanosine, pubmed-meshheading:17554210-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17554210-Glucose-6-Phosphatase, pubmed-meshheading:17554210-Glutathione, pubmed-meshheading:17554210-Insulin-Like Growth Factor II, pubmed-meshheading:17554210-Isoenzymes, pubmed-meshheading:17554210-Liver, pubmed-meshheading:17554210-Male, pubmed-meshheading:17554210-Metabolic Detoxication, Drug, pubmed-meshheading:17554210-Precancerous Conditions, pubmed-meshheading:17554210-Proto-Oncogene Proteins c-raf, pubmed-meshheading:17554210-Rats, pubmed-meshheading:17554210-Rats, Sprague-Dawley
pubmed:year
2007
pubmed:articleTitle
Changes in the antioxidant defense and hepatic drug metabolizing enzyme and isoenzyme levels, 8-hydroxydeoxyguanosine formation and expressions of c-raf.1 and insulin-like growth factor II genes during the stages of development of hepatocellular carcinoma in rats.
pubmed:affiliation
Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India. biswajit55@yahoo.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't