Document Detail


Activation of certain N-arylacetamides and N-arylacetohydroxamic acids in relation to mammary gland tumorigenesis in the rat.
MedLine Citation:
PMID:  6804871     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This report describes activation of certain N-aryl-acetamides and N-arylacetohydroxamic acids and its relationship to mammary gland tumorigenesis. Evidence is presented that metabolic activation of N-2-fluorenylacetamide (2-FAA) by mixed function oxidase of liver microsomes is the primary requirement for tumor induction in the mammary gland by this compound in young adult female rats. Mammary gland microsomes of those rats appear incapable of N-hydroxylating 2-FAA. Mammary gland microsomes of lactating rats, however, are capable of converting small amounts of 2-FAA to N-hydroxy-2-FAA, which suggests that the ability to perform certain metabolic activation reactions may depend on the stage of development of the mammary gland which is hormonally regulated. According to a current theory of chemical carcinogenesis, N-arylacetohydroxamic acids would have to be activated to electrophilic reactants to become ultimate carcinogens. Three mechanisms by which such reactants could be generated from N-aryl-acetohydroxamic acids in the mammary gland are reviewed: 1) nonenzymatic acetylation; 2) enzymatic N-O-acetyl transfer to form N-acetoxyarylamines; 3) one-electron oxidation to nitroxyl free radicals. In addition, the potential role of the metabolically formed glucuronide of N-hydroxy-2-FAA in mammary gland tumorigenesis is discussed.
Authors:
D Malejka-Giganti
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  National Cancer Institute monograph     Volume:  -     ISSN:  0083-1921     ISO Abbreviation:  Natl Cancer Inst Monogr     Publication Date:  1981 Dec 
Date Detail:
Created Date:  1982-07-08     Completed Date:  1982-07-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0216026     Medline TA:  Natl Cancer Inst Monogr     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  69-77     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
2-Acetylaminofluorene / analogs & derivatives*,  metabolism*
Adenocarcinoma / chemically induced
Adenofibroma / chemically induced
Adenoma / chemically induced
Animals
Biotransformation
Carcinogens*
Cytochromes / metabolism
Female
Hydroxyacetylaminofluorene / metabolism*
Mammary Neoplasms, Experimental / chemically induced*
Microsomes, Liver / metabolism*
Mixed Function Oxygenases / metabolism
NADPH-Ferrihemoprotein Reductase / metabolism
Rats
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
CA02571/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Carcinogens; 0/Cytochromes; 53-95-2/Hydroxyacetylaminofluorene; 53-96-3/2-Acetylaminofluorene; EC 1.-/Mixed Function Oxygenases; EC 1.6.2.4/NADPH-Ferrihemoprotein Reductase

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


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