| Activation of certain N-arylacetamides and N-arylacetohydroxamic acids in relation to mammary gland tumorigenesis in the rat. | |
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MedLine Citation:
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PMID: 6804871 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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D Malejka-Giganti |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: National Cancer Institute monograph Volume: - ISSN: 0083-1921 ISO Abbreviation: Natl Cancer Inst Monogr Publication Date: 1981 Dec |
Date Detail:
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Created Date: 1982-07-08 Completed Date: 1982-07-08 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0216026 Medline TA: Natl Cancer Inst Monogr Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 69-77 Citation Subset: IM |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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2-Acetylaminofluorene
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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:
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CA02571/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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