Document Detail

Role of O6-methylation in the initiation of GGTase-positive foci.
MedLine Citation:
PMID:  6130858     Owner:  NLM     Status:  MEDLINE    
The ability of seven methylating agents to form 7-methylguanine and O6-methylguanine was compared to their ability to initiate carcinogenesis as measured by the initiation of GGTase-positive foci. The seven methylating agents studied were methyl-N-nitroso-p-toluenesulfonamide (diazald), dimethylhydrazine (DMH), dimethylnitrosamine (DMN), dimethylsulfate (DMS), methyl methanesulfonate (MMS), methyl-N-nitro-N-nitrosoguanidine (MNNG) and methyl-N-nitrosourea (MNU). The DNA methylation and initiation of GGTase-positive foci was determined in partial hepatectomized rats. The formation of foci was promoted by 500 ppm sodium phenobarbital in the drinking water. While six of the seven compounds (DMH, DMN, DMS, MMS, MNNG and MNU) produced 7-methylguanine, only the four compounds (DMH, DMN, MNNG and MNU) that produced O6-methylguanine initiated GGTase-positive foci. The extent of O6-methylguanine produced by the methylating agents did not correspond with their potency to initiate GGTase-positive foci. Therefore, the initiation of GGTase-positive foci required the formation of O6-methylguanine. However, some sequential event altered the quantitative relationship of O6-methylguanine formation to the incidence of GGTase-positive foci.
M A Pereira; L H Lin; S L Herren
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  43     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  1983 Mar 
Date Detail:
Created Date:  1983-04-21     Completed Date:  1983-04-21     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  313-22     Citation Subset:  IM    
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MeSH Terms
Alkylating Agents / pharmacology*
Chromatography, High Pressure Liquid
DNA / metabolism*
Liver / enzymology*
Liver Regeneration
Rats, Inbred Strains
Structure-Activity Relationship
gamma-Glutamyltransferase / metabolism*
Reg. No./Substance:
0/Alkylating Agents; 9007-49-2/DNA; EC

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