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

TitleBenzo pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice.
Publication TypeJournal Article
Year of Publication2014
AuthorsZuo J, Brewer DS, Arlt VM, Cooper CS, Phillips DH
JournalBMC Genomics
Date Published10/2014
KeywordsAnimals, Benzo(a)pyrene, beta Catenin, Carcinogenesis, DNA Adducts, DNA Damage, Female, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Male, Mice, Mice, Inbred BALB C, MicroRNAs, Oligonucleotide Array Sequence Analysis, STAT3 Transcription Factor, Transcriptome, Tumor Suppressor Protein p53, Wnt Proteins

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.

Alternate JournalBMC Genomics
PubMed ID25297811
PubMed Central IDPMC4209037
Grant List / / Cancer Research UK / United Kingdom