| Pathobiologic and metabolic aspects of mammary gland tumorigenesis by N-substituted aryl compounds. | |
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MedLine Citation:
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PMID: 6339224 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Metabolic or synthetic N-hydroxylation of N-arylamides yields N-arylacylhydroxamic acids considerably more carcinogenic for the rat mammary gland than the parent amides both by systemic and topical administration. The size of the aryl moiety, the position of the nitrogen relative to the aryl moiety and the type of acyl group are determinants of the carcinogenic potency of N-arylacylhydroxamic acids. Induction of mammary tumors required ovarian hormones. Receptors for estrogen, androgen and progesterone were shown in the N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA)-induced mammary carcinoma. This tumor involved epithelial and stromal components of the mammary gland that were separated in culture and produced tumors of their respective origin in the isologous host. Both mammary epithelial cells and fibroblasts are capable of metabolism of carcinogens. The enzymes potentially involved in metabolic activation of N-arylamides and N-arylacylhydroxamic acids in the mammary gland include: a cytochrome P-450(P(1)-450) system, UDP-glucuronyltransferase, N,O-acyltransferases and peroxidases. Mammary microsomes in which cytochrome P(1)-450 was induced generated small amounts of N-OH-2-FAA from 2-FAA. N-OH-2-FAA and its carcinogenic isomer, N-OH-3-FAA, were oxidized by cytochrome c/H(2)O(2) to the nitroxyl free radicals which dismutated to the respective acetate esters and nitrosofluorenes. The addition of unsaturated lipid to either the free radicals or to the nitrosofluorenes gave electron spin resonance signals characteristic of immobilized radicals. It is proposed that interactions of carcinogens with lipids and with DNA play a role in mammary tumorigenesis. |
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Authors:
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D Malejka-Giganti; C L Ritter; C N Ryzewski |
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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.; Review |
Journal Detail:
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Title: Environmental health perspectives Volume: 49 ISSN: 0091-6765 ISO Abbreviation: Environ. Health Perspect. Publication Date: 1983 Mar |
Date Detail:
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Created Date: 1983-05-05 Completed Date: 1983-05-05 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0330411 Medline TA: Environ Health Perspect Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 175-83 Citation Subset: IM |
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| MeSH Terms | |
Descriptor/Qualifier:
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Amines
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metabolism,
toxicity* Animals Biotransformation Carcinogens / metabolism* Female Hydroxylation Lipid Metabolism Male Mammary Glands, Animal / enzymology Mammary Neoplasms, Experimental / chemically induced*, metabolism, pathology Microsomes, Liver / metabolism Mitochondria, Liver / metabolism Mixed Function Oxygenases / metabolism* Neoplasms, Hormone-Dependent / chemically induced Oxidoreductases / metabolism* Rats Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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CA-28000/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amines; 0/Carcinogens; EC 1.-/Mixed Function Oxygenases; EC 1.-/Oxidoreductases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
| Full Text | |
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Journal Information Journal ID (nlm-ta): Environ Health Perspect ISSN: 0091-6765 |
Article Information Download PDF  Print publication date: Month: 03 Year: 1983 Volume: 49First Page: 175 Last Page: 183 ID: 1569135 PubMed Id: 6339224 PubMed Id: 6339224 |
| Pathobiologic and metabolic aspects of mammary gland tumorigenesis by N-substituted aryl compounds | |
| D. Malejka-Giganti | |
| C. L. Ritter | |
| C. N. Ryzewski | |
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