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Benzo pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice.

Zuo J, Brewer DS, Arlt VM, Cooper CS, Phillips DH - BMC Genomics (2014)

Bottom Line: BaP-DNA adduct formation occurred in all six organs at levels that did not distinguish between target and non-target. cDNA microarray analysis showed a variety of genes modulated significantly by BaP in the six organs and the overall gene expression patterns were tissue specific.Additionally, several gene expression changes, such as in Trp53 activation and Stat3 activity suggested some similarities in molecular mechanisms in two target organs (lung and spleen), which were not found in the other four organs.Altogether, these findings showed that DNA adduct levels and early gene expression changes did not fully distinguish target from non-target organs.

View Article: PubMed Central - PubMed

Affiliation: Analytical and Environmental Sciences Division, MRC-PHE Centre for Environment & Health, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. david.phillips@kcl.ac.uk.

ABSTRACT

Background: Gene expression changes induced by carcinogens may identify differences in molecular function between target and non-target organs. Target organs for benzo[a]pyrene (BaP) carcinogenicity in mice (lung, spleen and forestomach) and three non-target organs (liver, colon and glandular stomach) were investigated for DNA adducts by 32P-postlabelling, for gene expression changes by cDNA microarray and for miRNA expression changes by miRNA microarray after exposure of animals to BaP.

Results: BaP-DNA adduct formation occurred in all six organs at levels that did not distinguish between target and non-target. cDNA microarray analysis showed a variety of genes modulated significantly by BaP in the six organs and the overall gene expression patterns were tissue specific. Gene ontology analysis also revealed that BaP-induced bioactivities were tissue specific; eight genes (Tubb5, Fos, Cdh1, Cyp1a1, Apc, Myc, Ctnnb1 and Cav) showed significant expression difference between three target and three non-target organs. Additionally, several gene expression changes, such as in Trp53 activation and Stat3 activity suggested some similarities in molecular mechanisms in two target organs (lung and spleen), which were not found in the other four organs. Changes in miRNA expression were generally tissue specific, involving, in total, 21/54 miRNAs significantly up- or down-regulated.

Conclusions: Altogether, these findings showed that DNA adduct levels and early gene expression changes did not fully distinguish target from non-target organs. However, mechanisms related to early changes in p53, Stat3 and Wnt/β-catenin pathways may play roles in defining BaP organotropism.

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Related in: MedlinePlus

Hierarchical cluster analysis(HCA)of 54 mouse miRNAs in 6 mouse organs. The female mice received 5 daily doses of 125 mg/kg b.wt/day of BaP by oral gavage. 6 organs were unsupervised clustered with Pearson’s correlation analysis. The results show tissue specific expression patterns (LU-lung, LI-liver, SP-spleen, CO-colon, GS-glandular stomach, FS-forestomach).
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Fig5: Hierarchical cluster analysis(HCA)of 54 mouse miRNAs in 6 mouse organs. The female mice received 5 daily doses of 125 mg/kg b.wt/day of BaP by oral gavage. 6 organs were unsupervised clustered with Pearson’s correlation analysis. The results show tissue specific expression patterns (LU-lung, LI-liver, SP-spleen, CO-colon, GS-glandular stomach, FS-forestomach).

Mentions: The expressions of 54 mouse miRNAs on the microarray were first analysed using hierarchical cluster analysis (Figure 5). The majority of changes of miRNA expressions pattern were distinct for each of the six organs and the target organs did not cluster separately from the non-target organs. Instead, the results indicate that the profiles of BaP-induced miRNA expression changes in the six mouse organs are tissue specific.Figure 5


Benzo pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice.

Zuo J, Brewer DS, Arlt VM, Cooper CS, Phillips DH - BMC Genomics (2014)

Hierarchical cluster analysis(HCA)of 54 mouse miRNAs in 6 mouse organs. The female mice received 5 daily doses of 125 mg/kg b.wt/day of BaP by oral gavage. 6 organs were unsupervised clustered with Pearson’s correlation analysis. The results show tissue specific expression patterns (LU-lung, LI-liver, SP-spleen, CO-colon, GS-glandular stomach, FS-forestomach).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4209037&req=5

Fig5: Hierarchical cluster analysis(HCA)of 54 mouse miRNAs in 6 mouse organs. The female mice received 5 daily doses of 125 mg/kg b.wt/day of BaP by oral gavage. 6 organs were unsupervised clustered with Pearson’s correlation analysis. The results show tissue specific expression patterns (LU-lung, LI-liver, SP-spleen, CO-colon, GS-glandular stomach, FS-forestomach).
Mentions: The expressions of 54 mouse miRNAs on the microarray were first analysed using hierarchical cluster analysis (Figure 5). The majority of changes of miRNA expressions pattern were distinct for each of the six organs and the target organs did not cluster separately from the non-target organs. Instead, the results indicate that the profiles of BaP-induced miRNA expression changes in the six mouse organs are tissue specific.Figure 5

Bottom Line: BaP-DNA adduct formation occurred in all six organs at levels that did not distinguish between target and non-target. cDNA microarray analysis showed a variety of genes modulated significantly by BaP in the six organs and the overall gene expression patterns were tissue specific.Additionally, several gene expression changes, such as in Trp53 activation and Stat3 activity suggested some similarities in molecular mechanisms in two target organs (lung and spleen), which were not found in the other four organs.Altogether, these findings showed that DNA adduct levels and early gene expression changes did not fully distinguish target from non-target organs.

View Article: PubMed Central - PubMed

Affiliation: Analytical and Environmental Sciences Division, MRC-PHE Centre for Environment & Health, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. david.phillips@kcl.ac.uk.

ABSTRACT

Background: Gene expression changes induced by carcinogens may identify differences in molecular function between target and non-target organs. Target organs for benzo[a]pyrene (BaP) carcinogenicity in mice (lung, spleen and forestomach) and three non-target organs (liver, colon and glandular stomach) were investigated for DNA adducts by 32P-postlabelling, for gene expression changes by cDNA microarray and for miRNA expression changes by miRNA microarray after exposure of animals to BaP.

Results: BaP-DNA adduct formation occurred in all six organs at levels that did not distinguish between target and non-target. cDNA microarray analysis showed a variety of genes modulated significantly by BaP in the six organs and the overall gene expression patterns were tissue specific. Gene ontology analysis also revealed that BaP-induced bioactivities were tissue specific; eight genes (Tubb5, Fos, Cdh1, Cyp1a1, Apc, Myc, Ctnnb1 and Cav) showed significant expression difference between three target and three non-target organs. Additionally, several gene expression changes, such as in Trp53 activation and Stat3 activity suggested some similarities in molecular mechanisms in two target organs (lung and spleen), which were not found in the other four organs. Changes in miRNA expression were generally tissue specific, involving, in total, 21/54 miRNAs significantly up- or down-regulated.

Conclusions: Altogether, these findings showed that DNA adduct levels and early gene expression changes did not fully distinguish target from non-target organs. However, mechanisms related to early changes in p53, Stat3 and Wnt/β-catenin pathways may play roles in defining BaP organotropism.

Show MeSH
Related in: MedlinePlus