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

Zuo, Jie, Brewer, Daniel, Arlt, Volker M, Cooper, Colin and Phillips, David H (2014) Benzo[a]pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice. BMC Genomics, 15. ISSN 1471-2164

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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.

Item Type: Article
Additional Information: © 2014 Zuo et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 08 Oct 2014 08:48
Last Modified: 27 Jul 2020 23:42
URI: https://ueaeprints.uea.ac.uk/id/eprint/50244
DOI: 10.1186/1471-2164-15-880

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