University of Louisville

Poster Title

Resveratrol Induces G1-Arrest in Response to Low-Level DNA Damage in Lung Cancer Cells

Institution

University of Louisville

Abstract

(+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) is a metabolized, carcinogenic polycyclic aromatic hydrocarbon that is a major cause of lung cancer. BPDE covalently binds to guanine in DNA and can cause mutations. At low levels of DNA damage that are still carcinogenic, a DNA repair response is weak or not activated. Studies show that resveratrol, a chemopreventive antioxidant, can reduce cancer induction by chemical carcinogens. Possible mechanisms include alteration of G1 arrest by enhanced induction of p53, which has been called the guardian of the genome, and p21, a protein responsible for G1 arrest. Dephosphorylation of retinoblastoma (RB) proteins could also cause the lung cancer cells to arrest in G1. Our hypothesis is that resveratrol will enhance the G1 arrest in response to DNA damage induced by BPDE. Western blot protein assays were used to test this hypothesis. The results showed that resveratrol did not alter the induction of p53 and p21 by BPDE. However, the BPDE dose-dependent dephosphorylation of RB was shifted to lower BPDE concentrations by resveratrol pre-treatments. These results suggest that resveratrol enhances G1 arrest in response to DNA damage thus allowing more time for DNA repair.

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Resveratrol Induces G1-Arrest in Response to Low-Level DNA Damage in Lung Cancer Cells

(+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) is a metabolized, carcinogenic polycyclic aromatic hydrocarbon that is a major cause of lung cancer. BPDE covalently binds to guanine in DNA and can cause mutations. At low levels of DNA damage that are still carcinogenic, a DNA repair response is weak or not activated. Studies show that resveratrol, a chemopreventive antioxidant, can reduce cancer induction by chemical carcinogens. Possible mechanisms include alteration of G1 arrest by enhanced induction of p53, which has been called the guardian of the genome, and p21, a protein responsible for G1 arrest. Dephosphorylation of retinoblastoma (RB) proteins could also cause the lung cancer cells to arrest in G1. Our hypothesis is that resveratrol will enhance the G1 arrest in response to DNA damage induced by BPDE. Western blot protein assays were used to test this hypothesis. The results showed that resveratrol did not alter the induction of p53 and p21 by BPDE. However, the BPDE dose-dependent dephosphorylation of RB was shifted to lower BPDE concentrations by resveratrol pre-treatments. These results suggest that resveratrol enhances G1 arrest in response to DNA damage thus allowing more time for DNA repair.