Document Detail

Immunocytochemical analysis of O6-alkylguanine shows tissue specific formation in and removal from esophageal and liver DNA in rats treated with methylbenzylnitrosamine, dimethylnitrosamine, diethylnitrosamine and ethylnitrosourea.
MedLine Citation:
PMID:  2660979     Owner:  NLM     Status:  MEDLINE    
The formation and repair of carcinogen-DNA adducts in esophagus and liver of rats treated with a single i.p. dose of methylbenzylnitrosamine (MBN), dimethylnitrosamine (DMN), diethylnitrosamine (DEN) or ethylnitrosourea (ENU) has been studied using peroxidase immunocytochemistry to visualize O6-alkylguanine in DNA of individual cells. After MBN O6-methylguanine (O6-MeG) specific nuclear staining was only present in the target tissue for tumor induction, the esophageal epithelium. Part of the adducts persisted for at least 72 h. No O6-MeG could be detected in liver. DEN, a carcinogen in liver and esophagus, led to DNA modification of esophageal epithelial cells, and liver parenchymal and non-parenchymal (Kupffer and sinusoidal) cells of the centrilobular area. O6-EtG was removed within 72 h from both liver cell populations. A similar distribution of adduct (O6-MeG) formation was observed in liver after the hepatocarcinogen DMN, but this nitrosamine did not detectably modify esophageal cells. O6-MeG persisted in Kupffer and especially sinusoidal lining cells of liver, consistent with the induction of sarcomas by DMN. The relatively unspecific, directly alkylating carcinogen ENU modified DNA of all cell types to a similar extent. A qualitative correlation was obtained between the tissue specific ability to induce tumors and the formation of O6-alkylguanine (O6-alkylG). Our experiments support the hypothesis that DNA modification is necessary for the initiation of carcinogenesis by chemical carcinogens, and that a low capacity to repair promutagenic lesions, like O6-alkylG, potentiates this process.
E Scherer; T Van Den Berg; E Vermeulen; H H Winterwerp; L Den Engelse
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer letters     Volume:  46     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  1989 Jul 
Date Detail:
Created Date:  1989-08-03     Completed Date:  1989-08-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  21-9     Citation Subset:  IM    
Division of Chemical Carcinogenesis, Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
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MeSH Terms
Carcinogens / toxicity*
Cell Nucleus / metabolism
DNA Damage*
DNA Repair
Diethylnitrosamine / toxicity
Dimethylnitrosamine / analogs & derivatives,  toxicity
Esophagus / metabolism*,  ultrastructure
Ethylnitrosourea / toxicity
Guanine / analogs & derivatives*,  analysis
Immunoenzyme Techniques
Liver / metabolism*,  ultrastructure
Methyltransferases / metabolism
O(6)-Methylguanine-DNA Methyltransferase
Rats, Inbred Strains
Substrate Specificity
Reg. No./Substance:
0/Carcinogens; 20535-83-5/O-(6)-methylguanine; 51866-19-4/6-ethylguanine; 55-18-5/Diethylnitrosamine; 62-75-9/Dimethylnitrosamine; 73-40-5/Guanine; 759-73-9/Ethylnitrosourea; 937-40-6/nitrosobenzylmethylamine; EC 2.1.1.-/Methyltransferases; EC Methyltransferase

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

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