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

Jie Zuo, Daniel S Brewer, Volker M Arlt

  • 1Analytical 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.

BMC Genomics
|October 10, 2014
PubMed
Abstract

Insights

Benzo[a]pyrene (BaP) carcinogenicity targets organs differently. While DNA adducts and early gene expression didn't fully distinguish target from non-target organs, specific pathway changes suggest roles in BaP organotropism.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Carcinogenesis

Background:

  • Carcinogen-induced gene expression can reveal molecular differences between target and non-target organs.
  • Benzo[a]pyrene (BaP) is a known carcinogen with specific target organs in mice.

Purpose of the Study:

  • To investigate DNA adducts, gene expression, and miRNA expression in BaP target and non-target organs.
  • To identify molecular mechanisms underlying BaP organotropism.

Main Methods:

  • 32P-postlabeling for DNA adducts.
  • cDNA microarray for gene expression analysis.
  • miRNA microarray for miRNA expression profiling.

Main Results:

  • BaP-DNA adducts were found in all organs, not differentiating target from non-target.
  • Gene expression patterns were tissue-specific, with eight genes showing significant differences between target and non-target organs.
  • miRNA expression changes were largely tissue-specific, with 21 out of 54 miRNAs significantly altered.

Conclusions:

  • Early DNA adduct levels and gene expression changes did not fully distinguish BaP target from non-target organs.
  • Early alterations in p53, Stat3, and Wnt/β-catenin pathways may contribute to BaP's organ-specific toxicity.

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