beta-carotene-induced changes in RARbeta isoform mRNA expression patterns do not influence lung adenoma multiplicity in the NNK-initiated A/J mouse model.

2.50
Hdl Handle:
http://hdl.handle.net/10146/52594
Title:
beta-carotene-induced changes in RARbeta isoform mRNA expression patterns do not influence lung adenoma multiplicity in the NNK-initiated A/J mouse model.
Authors:
Goralczyk, Regina; Bachmann, Heinrich; Wertz, Karin; Lenz, Barbara; Riss, Georges; Buchwald Hunziker, Petra; Greatrix, Brad; Aebischer, Claude-Pierre
Abstract:
A number of epidemiological studies have reported associations of beta-carotene plasma levels or intake with decreased lung cancer risk. However, intervention studies in smokers reported increased lung tumor rates after high long-term beta-carotene supplementation. For insight into these conflicting results, we studied the influence of beta-carotene on tobacco smoke carcinogen-induced lung cancer development in the A/J-mouse using 4-(N-Methyl-N-nitro samino)-1-(3-pyridyl)-1-butanone (NNK) as the initiator and lung adenoma multiplicity as the functional endpoint. Gene regulation of the putative tumor suppressor RARbeta in mouse lung was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for its relevance in predicting the endpoint of lung cancer. A/J-mice achieved plasma beta-carotene levels of up to 3 micromol/L within 4 wk and up to 6 micromol/L after 6 mo of supplementation on a diet modified to enhance beta-carotene absorption. Despite high lung beta-carotene concentrations of up to 6 micromol/kg, tumor multiplicity was not significantly affected by the beta-carotene treatment, either in carcinogen-initiated or non-initiated mice, and was unrelated to beta-carotene dose and the time point of treatment during cancer formation. Tumor multiplicity did not correlate with beta-carotene plasma levels in NNK-treated animals. All RARbeta isoforms were significantly suppressed in the lungs of NNK- and NNK plus high dose beta-carotene-treated animals. However, the number of tumors per mouse did not correlate with the RARbeta-isoform expression levels. beta-carotene alone after 3 mo of supplementation mildly but significantly increased levels of RARbeta1, beta2, and beta4. This increase persisted for 6 mo for RARbeta2 and beta4. In summary, we found no effect of beta-carotene on tumor formation in the NNK-initiated A/J-mouse lung cancer model with respect to dose or time point of treatment. beta-Carotene-induced changes in RARbeta isoform gene expression levels were not predictive for the number of lung tumors but were indicative of intact beta-carotene metabolism and persistent sensitivity to retinoic acid in the mice. Down-regulation of RARbeta in NNK-induced adenoma-bearing lungs was similar to that observed in human lung cancer and further confirms the A/J-mouse as a valuable model for lung carcinogenesis.
Citation:
Nutr. Cancer 2006, 54 (2):252-262
Journal:
Nutrition and Cancer
Issue Date:
2006
URI:
http://hdl.handle.net/10146/52594
DOI:
10.1207/s15327914nc5402_12
PubMed ID:
16898870
Additional Links:
http://www.informaworld.com/smpp/content~content=a785829701~db=all~order=page
Type:
Article
Language:
en
Description:
Dietary modulation of cancer & cancer biomarkers; Dietary modulation of carcinogenesis-related pathways. Dietary item or component studied: beta-carotene Outcome studied: lung adenoma; gene regulation of the putative tumor suppressor RARbeta in mouse lung. Study type: A/J-mice Tissue/biological material/sample size: lung; blood. Mode of exposure: dietaryImpact on outcome (including dose-response): Despite high lung beta-carotene concentrations of up to 6 micromol/kg, tumor multiplicity was not significantly affected by the beta-carotene treatment, either in carcinogen-initiated or non-initiated mice, and was unrelated to beta-carotene dose and the time point of treatment during cancer formation. Tumor multiplicity did not correlate with beta-carotene plasma levels in NNK-treated animals. All RARbeta isoforms were significantly suppressed in the lungs of NNK- and NNK plus high dose beta-carotene-treated animals. However, the number of tumors per mouse did not correlate with the RARbeta-isoform expression levels. beta-carotene alone after 3 mo of supplementation mildly but significantly increased levels of RARbeta1, beta2, and beta4. This increase persisted for 6 mo for RARbeta2 and beta4. Keywords - classification: Adenoma;administration & dosage;adverse effects;Animals;beta Carotene;blood;Carcinogens;chemically induced;chemistry;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;Dietary Supplements;Disease Models,Animal;Dose-Response Relationship,Drug;drug effects;Human;Humans;Lung;Lung Neoplasms;Male;metabolism;Mice;Nitrosamines;pathology;pharmacology;prevention & control;Protein Isoforms;Random Allocation;Receptors,Retinoic Acid;Research;Reverse Transcriptase Polymerase Chain Reaction;RNA,Messenger;Smoking;toxicity;Vitamins;
ISSN:
0163-5581
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorGoralczyk, Regina-
dc.contributor.authorBachmann, Heinrich-
dc.contributor.authorWertz, Karin-
dc.contributor.authorLenz, Barbara-
dc.contributor.authorRiss, Georges-
dc.contributor.authorBuchwald Hunziker, Petra-
dc.contributor.authorGreatrix, Brad-
dc.contributor.authorAebischer, Claude-Pierre-
dc.date.accessioned2009-03-06T11:11:43Z-
dc.date.available2009-03-06T11:11:43Z-
dc.date.issued2006-
dc.identifier.citationNutr. Cancer 2006, 54 (2):252-262en
dc.identifier.issn0163-5581-
dc.identifier.pmid16898870-
dc.identifier.doi10.1207/s15327914nc5402_12-
dc.identifier.urihttp://hdl.handle.net/10146/52594-
dc.descriptionDietary modulation of cancer & cancer biomarkers; Dietary modulation of carcinogenesis-related pathways. Dietary item or component studied: beta-carotene Outcome studied: lung adenoma; gene regulation of the putative tumor suppressor RARbeta in mouse lung. Study type: A/J-mice Tissue/biological material/sample size: lung; blood. Mode of exposure: dietaryImpact on outcome (including dose-response): Despite high lung beta-carotene concentrations of up to 6 micromol/kg, tumor multiplicity was not significantly affected by the beta-carotene treatment, either in carcinogen-initiated or non-initiated mice, and was unrelated to beta-carotene dose and the time point of treatment during cancer formation. Tumor multiplicity did not correlate with beta-carotene plasma levels in NNK-treated animals. All RARbeta isoforms were significantly suppressed in the lungs of NNK- and NNK plus high dose beta-carotene-treated animals. However, the number of tumors per mouse did not correlate with the RARbeta-isoform expression levels. beta-carotene alone after 3 mo of supplementation mildly but significantly increased levels of RARbeta1, beta2, and beta4. This increase persisted for 6 mo for RARbeta2 and beta4. Keywords - classification: Adenoma;administration & dosage;adverse effects;Animals;beta Carotene;blood;Carcinogens;chemically induced;chemistry;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;Dietary Supplements;Disease Models,Animal;Dose-Response Relationship,Drug;drug effects;Human;Humans;Lung;Lung Neoplasms;Male;metabolism;Mice;Nitrosamines;pathology;pharmacology;prevention & control;Protein Isoforms;Random Allocation;Receptors,Retinoic Acid;Research;Reverse Transcriptase Polymerase Chain Reaction;RNA,Messenger;Smoking;toxicity;Vitamins;en
dc.description.abstractA number of epidemiological studies have reported associations of beta-carotene plasma levels or intake with decreased lung cancer risk. However, intervention studies in smokers reported increased lung tumor rates after high long-term beta-carotene supplementation. For insight into these conflicting results, we studied the influence of beta-carotene on tobacco smoke carcinogen-induced lung cancer development in the A/J-mouse using 4-(N-Methyl-N-nitro samino)-1-(3-pyridyl)-1-butanone (NNK) as the initiator and lung adenoma multiplicity as the functional endpoint. Gene regulation of the putative tumor suppressor RARbeta in mouse lung was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for its relevance in predicting the endpoint of lung cancer. A/J-mice achieved plasma beta-carotene levels of up to 3 micromol/L within 4 wk and up to 6 micromol/L after 6 mo of supplementation on a diet modified to enhance beta-carotene absorption. Despite high lung beta-carotene concentrations of up to 6 micromol/kg, tumor multiplicity was not significantly affected by the beta-carotene treatment, either in carcinogen-initiated or non-initiated mice, and was unrelated to beta-carotene dose and the time point of treatment during cancer formation. Tumor multiplicity did not correlate with beta-carotene plasma levels in NNK-treated animals. All RARbeta isoforms were significantly suppressed in the lungs of NNK- and NNK plus high dose beta-carotene-treated animals. However, the number of tumors per mouse did not correlate with the RARbeta-isoform expression levels. beta-carotene alone after 3 mo of supplementation mildly but significantly increased levels of RARbeta1, beta2, and beta4. This increase persisted for 6 mo for RARbeta2 and beta4. In summary, we found no effect of beta-carotene on tumor formation in the NNK-initiated A/J-mouse lung cancer model with respect to dose or time point of treatment. beta-Carotene-induced changes in RARbeta isoform gene expression levels were not predictive for the number of lung tumors but were indicative of intact beta-carotene metabolism and persistent sensitivity to retinoic acid in the mice. Down-regulation of RARbeta in NNK-induced adenoma-bearing lungs was similar to that observed in human lung cancer and further confirms the A/J-mouse as a valuable model for lung carcinogenesis.en
dc.language.isoenen
dc.relation.urlhttp://www.informaworld.com/smpp/content~content=a785829701~db=all~order=pageen
dc.subject.meshAdenoma-
dc.subject.meshAnimals-
dc.subject.meshCarcinogens-
dc.subject.meshDietary Supplements-
dc.subject.meshDisease Models, Animal-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshHumans-
dc.subject.meshLung-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshNitrosamines-
dc.subject.meshProtein Isoforms-
dc.subject.meshRNA, Messenger-
dc.subject.meshRandom Allocation-
dc.subject.meshReceptors, Retinoic Acid-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshSmoking-
dc.subject.meshVitamins-
dc.subject.meshbeta Carotene-
dc.titlebeta-carotene-induced changes in RARbeta isoform mRNA expression patterns do not influence lung adenoma multiplicity in the NNK-initiated A/J mouse model.en
dc.typeArticleen
dc.identifier.journalNutrition and Canceren
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