Deficient repair of DNA lesion O6-methylguanine in cirrhosis.
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.
Collier
J D
JD
Department of Medicine, Medical School, University of Newcastle upon Tyne, UK.
Guo
K
K
Burt
A D
AD
Bassendine
M F
MF
Major
G N
GN
D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology; D015984:Causality; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004260:DNA Repair; D005069:Evaluation Studies as Topic; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000473:pathology*; D008107:Liver Diseases / Q000097:blood / Q000145:classification / Q000473:pathology*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology; D008214:Lymphocytes / Q000737:chemistry*; D016296:Mutagenesis; D012307:Risk Factors
D006147:Guanine; C008449:O-(6)-methylguanine