Abstract
Abstract Our previous findings demonstrated that DNA damage by polynuclear aromatic hydrocarbons (PAHs) triggers cellular protective response of cell growth inhibition (G1-S cell cycle arrest and inhibition of DNA synthesis) in human fibroblast associated with accumulation of p53 protein, a known cell growth inhibitory transcription factor. Here we report that in different cell lines BPDE treatment (ultimate carcinogenic metabolite of the PAH benzo[a]pyrene) triggers variable extent of cell growth inhibition which do not correspond to the extent of increased p53 accumulation as we observed. We also observed that BPDE treatment of cells significantly down-regulates expression of p34cdc2, a known cell cycle activating protein. Although the role of cdc2 down-regulation in inhibition of cell cycle progression is well known, to the best of our knowledge cdc2 down-regulation in response to cellular insult by PAHs has not been reported. Unlike p53 accumulation there is correspondence between extent of cell growth inhibition and the extent of cdc2 down-regulation by BPDE in different cell lines. Interestingly, BPDE-induced cdc2 down-regulation is observed to be p53 dependent although there is lack of correspondence between the extent of p53 accumulation and cdc2 down-regulation. However, extent of BPDE induced cdc2 down-regulation was observed to have correspondence with the extent of accumulation of cell cycle inhibitor protein p21 (transactivation product of p53) in different cell lines. These findings may have an implication that cell growth inhibition in response to DNA damaging PAHs may involve down-regulation of cdc2 protein mediated by p53 activation (transactivation ability), and the extent of p53 accumulation is not the determining factor in this regard. Citation Format: Jagat J. Mukherjee, Subodh Kumar. Benzopyrene diol epoxide attenuates p34cdc2 and inhibits cell growth: role of p53. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3586. doi:10.1158/1538-7445.AM2013-3586
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