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Event Title
Benzopyrene Diol Epoxide Induced Cell Growth Inhibition is Associated with Down-regulation of p34cdc2: Role of p53
Start Date
25-10-2012 11:00 AM
Description
Abstract DNA damage by polynuclear aromatic hydrocarbons (PAHs) is known to trigger cellular protective response of cell growth inhibition. In this regard our previous observation showed G1-S cell cycle arrest (inhibition of DNA synthesis) in human fibroblast associated with accumulation of p53 protein, a known cell growth inhibitory transcription factor, in response to treatment with BPDE (ultimate carcinogenic metabolite of the PAH benzo[a]pyrene). Here we report that BPDE treatment triggers variable extent of cell growth inhibition in different cell lines, and the extent of cell growth inhibition in different cell lines do not correspond to the extent of increased p53 accumulation as opposed to our expectation. 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. We observed correspondence between extent of cell growth inhibition and the extent of cdc2 down-regulation by BPDE in different cell lines as opposed to p53 accumulation as mentioned above. Interestingly, BPDE-mediated cdc2 down-regulation is observed to be p53 dependent although extent of p53 accumulation does not correspond to the extent of cdc2 down-regulation. However, the extent of cdc2 down-regulation corresponds to 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 elicited by p53 activation (transactivation ability), and the extent of p53 accumulation is not the determining factor in this regard.
Benzopyrene Diol Epoxide Induced Cell Growth Inhibition is Associated with Down-regulation of p34cdc2: Role of p53
Abstract DNA damage by polynuclear aromatic hydrocarbons (PAHs) is known to trigger cellular protective response of cell growth inhibition. In this regard our previous observation showed G1-S cell cycle arrest (inhibition of DNA synthesis) in human fibroblast associated with accumulation of p53 protein, a known cell growth inhibitory transcription factor, in response to treatment with BPDE (ultimate carcinogenic metabolite of the PAH benzo[a]pyrene). Here we report that BPDE treatment triggers variable extent of cell growth inhibition in different cell lines, and the extent of cell growth inhibition in different cell lines do not correspond to the extent of increased p53 accumulation as opposed to our expectation. 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. We observed correspondence between extent of cell growth inhibition and the extent of cdc2 down-regulation by BPDE in different cell lines as opposed to p53 accumulation as mentioned above. Interestingly, BPDE-mediated cdc2 down-regulation is observed to be p53 dependent although extent of p53 accumulation does not correspond to the extent of cdc2 down-regulation. However, the extent of cdc2 down-regulation corresponds to 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 elicited by p53 activation (transactivation ability), and the extent of p53 accumulation is not the determining factor in this regard.