Dietary effects of soy isoflavones daidzein and genistein on 7,12-dimethylbenz[a]anthracene-induced mammary mutagenesis and carcinogenesis in ovariectomized Big Blue transgenic rats.

2.50
Hdl Handle:
http://hdl.handle.net/10146/68538
Title:
Dietary effects of soy isoflavones daidzein and genistein on 7,12-dimethylbenz[a]anthracene-induced mammary mutagenesis and carcinogenesis in ovariectomized Big Blue transgenic rats.
Authors:
Manjanatha, Mugimane; Shelton, Sharon; Bishop, Michelle; Lyn-Cook, Lascelles; Aidoo, Anane
Abstract:
The major constituents of isoflavones daidzein (DZ) and genistein (GE) interact with the and estrogen receptors in several tissues including mammary tissues. In this study, we used ovariectomy (OVX) to model menopause and determined the effects of DZ, GE or 17beta-estradiol (E(2)) exposures on chemically induced mutagenesis and carcinogenesis in the mammary glands of female Big Blue transgenic rats. The rats were fed control diet containing the isoflavones and E(2) and treated with a single oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) at PND50. Animals were euthanized at 16 or 20 weeks post-carcinogen treatment to assess mutant frequencies (MFs) and histopathological parameters, respectively. The isoflavones or E(2) supplementation alone resulted in the lac I MFs that were not significantly different from the MFs measured in rats fed the control diet alone. DMBA exposure, however, induced significant increases in the lac I MFs in the mammary tissues of both OVX and INT rats and Hprt MFs in spleen lymphocytes (P < 0.01). In general, feeding the isoflavones or E(2) did not cause any significant changes in DMBA-induced mutagenicity in the mammary tissues. However, feeding the isoflavone mixture (daidzein + genistein; DZG) resulted in a significant reduction in the DMBA-induced lac I MFs (P < 0.05). Cell proliferation as measured by PCNA immunohistochemistry was increased in both OVX and INT rats exposed to DMBA as compared with rats fed control diet (P < 0.05). Mammary histology indicated that hyperplasia was induced in most of the treatment groups including control. Although DMBA did not induce mammary tumors in the OVX rats, adenoma and adenocarcinoma were detected in the mammary glands of INT rats.
Citation:
Carcinogenesis 2006, 27 (10):1970-1979
Journal:
Carcinogenesis
Issue Date:
Oct-2006
URI:
http://hdl.handle.net/10146/68538
DOI:
10.1093/carcin/bgl028
PubMed ID:
16709578
Additional Links:
http://carcin.oxfordjournals.org/cgi/content/full/27/10/1970; Corrected and republished in: Carcinogenesis. 2006 Dec;27(12):2555-64. http://carcin.oxfordjournals.org/cgi/content/full/27/12/2555
Type:
Article
Language:
en
Description:
Dietary modulation of cancer & cancer biomarkers. Dietary item or component studied: the isoflavones daidzein (DZ) and genistein (GE)Outcome studied: Mammary gland hyperplasia; DNA damage. Study type: Big Blue transgenic rats Tissue/biological material/sample size: mammary glands; lymphocytes isolated from the spleen. Mode of exposure: dietary. Impact on outcome (including dose-response): The isoflavones or E(2) supplementation alone resulted in the lac I MFs that were not significantly different from the MFs measured in rats fed the control diet alone. DMBA exposure, however, induced significant increases in the lac I MFs in the mammary tissues of both OVX and INT rats and Hprt MFs in spleen lymphocytes (P < 0.01). In general, feeding the isoflavones or E(2) did not cause any significant changes in DMBA-induced mutagenicity in the mammary tissues. However, feeding the isoflavone mixture (daidzein + genistein; DZG) resulted in a significant reduction in the DMBA-induced lac I MFs (P < 0.05). Cell proliferation as measured by PCNA immunohistochemistry was increased in both OVX and INT rats exposed to DMBA as compared with rats fed control diet (P < 0.05). Mammary histology indicated that hyperplasia was induced in most of the treatment groups including control. Although DMBA did not induce mammary tumors in the OVX rats, adenoma and adenocarcinoma were detected in the mammary glands of INT rats. KEYWORD CLASSIFICATION: 9,10-Dimethyl-1,2-benzanthracene;administration & dosage;analysis;Animals;Animals,Genetically Modified;Apoptosis;Body Weight;chemically induced;Diet;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;drug effects;Female;genetics;Genistein;humans;Hypoxanthine Phosphoribosyltransferase;Isoflavones;Lac Operon;lymphocytes;Mammary Glands,Animal;Mammary Neoplasms,Experimental;Mutation;Organ Size;Ovariectomy;pathology;prevention & control;Proliferating Cell Nuclear Antigen;Rats;Rats,Inbred BB;Research;Toxicology;
ISSN:
0143-3334
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorManjanatha, Mugimane-
dc.contributor.authorShelton, Sharon-
dc.contributor.authorBishop, Michelle-
dc.contributor.authorLyn-Cook, Lascelles-
dc.contributor.authorAidoo, Anane-
dc.date.accessioned2009-05-19T08:43:11Z-
dc.date.available2009-05-19T08:43:11Z-
dc.date.issued2006-10-
dc.identifier.citationCarcinogenesis 2006, 27 (10):1970-1979en
dc.identifier.issn0143-3334-
dc.identifier.pmid16709578-
dc.identifier.doi10.1093/carcin/bgl028-
dc.identifier.urihttp://hdl.handle.net/10146/68538-
dc.descriptionDietary modulation of cancer & cancer biomarkers. Dietary item or component studied: the isoflavones daidzein (DZ) and genistein (GE)Outcome studied: Mammary gland hyperplasia; DNA damage. Study type: Big Blue transgenic rats Tissue/biological material/sample size: mammary glands; lymphocytes isolated from the spleen. Mode of exposure: dietary. Impact on outcome (including dose-response): The isoflavones or E(2) supplementation alone resulted in the lac I MFs that were not significantly different from the MFs measured in rats fed the control diet alone. DMBA exposure, however, induced significant increases in the lac I MFs in the mammary tissues of both OVX and INT rats and Hprt MFs in spleen lymphocytes (P < 0.01). In general, feeding the isoflavones or E(2) did not cause any significant changes in DMBA-induced mutagenicity in the mammary tissues. However, feeding the isoflavone mixture (daidzein + genistein; DZG) resulted in a significant reduction in the DMBA-induced lac I MFs (P < 0.05). Cell proliferation as measured by PCNA immunohistochemistry was increased in both OVX and INT rats exposed to DMBA as compared with rats fed control diet (P < 0.05). Mammary histology indicated that hyperplasia was induced in most of the treatment groups including control. Although DMBA did not induce mammary tumors in the OVX rats, adenoma and adenocarcinoma were detected in the mammary glands of INT rats. KEYWORD CLASSIFICATION: 9,10-Dimethyl-1,2-benzanthracene;administration & dosage;analysis;Animals;Animals,Genetically Modified;Apoptosis;Body Weight;chemically induced;Diet;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;drug effects;Female;genetics;Genistein;humans;Hypoxanthine Phosphoribosyltransferase;Isoflavones;Lac Operon;lymphocytes;Mammary Glands,Animal;Mammary Neoplasms,Experimental;Mutation;Organ Size;Ovariectomy;pathology;prevention & control;Proliferating Cell Nuclear Antigen;Rats;Rats,Inbred BB;Research;Toxicology;en
dc.description.abstractThe major constituents of isoflavones daidzein (DZ) and genistein (GE) interact with the and estrogen receptors in several tissues including mammary tissues. In this study, we used ovariectomy (OVX) to model menopause and determined the effects of DZ, GE or 17beta-estradiol (E(2)) exposures on chemically induced mutagenesis and carcinogenesis in the mammary glands of female Big Blue transgenic rats. The rats were fed control diet containing the isoflavones and E(2) and treated with a single oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) at PND50. Animals were euthanized at 16 or 20 weeks post-carcinogen treatment to assess mutant frequencies (MFs) and histopathological parameters, respectively. The isoflavones or E(2) supplementation alone resulted in the lac I MFs that were not significantly different from the MFs measured in rats fed the control diet alone. DMBA exposure, however, induced significant increases in the lac I MFs in the mammary tissues of both OVX and INT rats and Hprt MFs in spleen lymphocytes (P < 0.01). In general, feeding the isoflavones or E(2) did not cause any significant changes in DMBA-induced mutagenicity in the mammary tissues. However, feeding the isoflavone mixture (daidzein + genistein; DZG) resulted in a significant reduction in the DMBA-induced lac I MFs (P < 0.05). Cell proliferation as measured by PCNA immunohistochemistry was increased in both OVX and INT rats exposed to DMBA as compared with rats fed control diet (P < 0.05). Mammary histology indicated that hyperplasia was induced in most of the treatment groups including control. Although DMBA did not induce mammary tumors in the OVX rats, adenoma and adenocarcinoma were detected in the mammary glands of INT rats.en
dc.language.isoenen
dc.relation.urlhttp://carcin.oxfordjournals.org/cgi/content/full/27/10/1970en
dc.relation.urlCorrected and republished in: Carcinogenesis. 2006 Dec;27(12):2555-64. http://carcin.oxfordjournals.org/cgi/content/full/27/12/2555en
dc.subject.mesh9,10-Dimethyl-1,2-benzanthracene-
dc.subject.meshAnimals-
dc.subject.meshAnimals, Genetically Modified-
dc.subject.meshApoptosis-
dc.subject.meshBody Weight-
dc.subject.meshDiet-
dc.subject.meshFemale-
dc.subject.meshGenistein-
dc.subject.meshHypoxanthine Phosphoribosyltransferase-
dc.subject.meshIsoflavones-
dc.subject.meshLac Operon-
dc.subject.meshMammary Glands, Animal-
dc.subject.meshMammary Neoplasms, Experimental-
dc.subject.meshMutation-
dc.subject.meshOrgan Size-
dc.subject.meshOvariectomy-
dc.subject.meshProliferating Cell Nuclear Antigen-
dc.subject.meshRats-
dc.subject.meshRats, Inbred BB-
dc.titleDietary effects of soy isoflavones daidzein and genistein on 7,12-dimethylbenz[a]anthracene-induced mammary mutagenesis and carcinogenesis in ovariectomized Big Blue transgenic rats.en
dc.typeArticleen
dc.identifier.journalCarcinogenesisen
All Items in ECNIS-NIOM are protected by copyright, with all rights reserved, unless otherwise indicated.