Document Detail

Deficient repair of DNA lesion O6-methylguanine in cirrhosis.
MedLine Citation:
PMID:  8093500     Owner:  NLM     Status:  MEDLINE    
Cirrhosis is a risk factor for hepatocellular carcinoma. O6-methylguanine is a promutagenic and potentially carcinogenic DNA lesion produced by environmental alkylating agents. If it is not repaired, DNA replication can lead to a G-to-A transition mutation, which is a known mechanism of oncogene activation. We have found that the activity of the repairing methyltransferase enzyme is significantly lower in cirrhotic tissue than in non-cirrhotic diseased liver or in normal liver. This finding suggests a mechanism for cirrhosis being a risk factor for cancer of the liver: increased cellular proliferation together with persistence of O6-methylguanine might lead to malignant transformation of liver cells through mutation and oncogene activation.
J D Collier; K Guo; A D Burt; M F Bassendine; G N Major
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  341     ISSN:  0140-6736     ISO Abbreviation:  Lancet     Publication Date:  1993 Jan 
Date Detail:
Created Date:  1993-02-11     Completed Date:  1993-02-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  207-8     Citation Subset:  AIM; IM    
Department of Medicine, Medical School, University of Newcastle upon Tyne, UK.
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MeSH Terms
Carcinoma, Hepatocellular / epidemiology,  etiology
Cell Division
Cell Transformation, Neoplastic
DNA Repair*
Evaluation Studies as Topic
Guanine / analogs & derivatives*,  chemistry
Liver Cirrhosis / blood,  complications,  pathology*
Liver Diseases / blood,  classification,  pathology*
Liver Neoplasms / epidemiology,  etiology
Lymphocytes / chemistry*
Risk Factors
Reg. No./Substance:
20535-83-5/O-(6)-methylguanine; 73-40-5/Guanine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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