Abstract
BackgroundGene 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.ResultsBaP-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.ConclusionsAltogether, 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-880) contains supplementary material, which is available to authorized users.
Highlights
Gene expression changes induced by carcinogens may identify differences in molecular function between target and non-target organs
Balb/c mice were treated with multiple carcinogenic doses of benzo[a]pyrene (BaP), after which DNA adduct levels and gene and miRNA expression changes were measured in three target organs and three non-target organs
In an investigation of the early changes induced in mouse organs exposed to a carcinogen, we determined whether DNA adduct formation, mRNA or miRNA expression can distinguish those mouse organs that are targets for BaP carcinogenesis from three organs that are non-targets
Summary
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. In the present study we have tested the hypothesis that carcinogen-induced changes in gene expression or miRNA expression may distinguish target organs from non-target ones. Balb/c mice were treated with multiple carcinogenic doses of benzo[a]pyrene (BaP), after which DNA adduct levels and gene and miRNA expression changes were measured in three target organs (lung, spleen and forestomach) and three non-target organs (liver, colon and glandular stomach). The results shed new light on the complexity of the mechanism of BaP carcinogenicity and identify some responses that may determine the carcinogen’s organotropism
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