Benzopyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice

BMC Genomics

David H Phillips²  Colin S Cooper³  Volker M Arlt²  Daniel S Brewer⁴  Jie Zuo¹ 

[1] Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford, OX3 9DS, UK;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;The Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK;School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK

关键词: miRNA;    Microarray;    Gene expression;    DNA adducts;    Benzo[a]pyrene;    Organotropism;    Carcinogenicity;   

Others  :  1128476
DOI  :  10.1186/1471-2164-15-880

 received in 2014-03-07, accepted in 2014-09-23,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Zuo et al.; licensee BioMed Central Ltd.

【 图 表 】

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