Benzo[a]Pyrene (B[a]P) is the most common PAH studied.  The metabolic product of B[a]P, B[a]P-7,8-dione (BPQ) damages DNA by  the generation of reactive oxygen species (ROS).  Two DNA repair genes in the BER pathway that repair oxidative damaged are OGG1 and APN1.  To determine the role of OGG1 and APN1 in BPQ induced mutagenesis, we knocked out both genes in a yeast mutagenesis system for p53.  We found that there was an increase in the mutation frequency and the number of of G:C/ T:A transversions in p53 treated with BPQ in ogg1 yeast but the loss of APN1 had no effect.  In addition we did not find a strand bias on p53 treated with BPQ in ogg1 yeast.  These studies suggest that OGG1 is essential in repairing oxidative damage caused by ROS and that the stand bias seen in lung cancer may not be due to the repair of oxidative lesions.

Role of base excision repair genes OGG1 and APN1 in B[a]P-7,8-dione induced p53 mutagenesis

244th National Meeting (2012)

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