Involvement of DNA polymerase β overexpression in the malignant transformation induced by benzo[a]pyrene

Toxicology. 2013 Jul 5:309:73-80. doi: 10.1016/j.tox.2013.04.017. Epub 2013 May 4.


Objective: To explore the relationship between DNA polymerase β (pol β) overexpression and benzo[a]pyrene (BaP) carcinogenesis.

Methods: Firstly, mouse embryonic fibroblasts that express wild-type level of DNA polymerase β (pol β cell) and high level of pol β (pol β oe cell) were treated by various concentrations of BaP to determine genetic instability induced by BaP under differential expression levels of pol β. Secondly, malignant transformation of pol β cells by low concentration of BaP (20 μM) was determined by soft agar colony formation assay and transformation focus assay. Thirdly, the mRNA and protein levels of BaP-transformed pol β cells (named pol β-T cells) was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot, and the genetic instability of these cells were examined by HPRT gene mutation assay and random amplified polymorphic DNA (RAPD) assay.

Results: Pol β cells were successfully transformed into malignant pol β-T cells by an exposure to low concentration of BaP for 6 months. Pol β-T cells exhibited increased levels of pol β gene expression, HPRT gene mutation frequency and polymorphisms of RAPD products that were comparable to those of pol β oe cells.

Conclusion: Pol β overexpression and its-associated genetic instability may play a key role in BaP carcinogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzo(a)pyrene / toxicity*
  • DNA Polymerase beta / biosynthesis*
  • DNA Polymerase beta / genetics*
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology*
  • Fibroblasts / pathology*
  • Gene Expression Regulation, Enzymologic*
  • Mice
  • Random Allocation


  • Benzo(a)pyrene
  • DNA Polymerase beta