title: Benzo[a]pyrene-induced DNA damage and p53 modulation in human hepatoma HepG2 cells for the identification of potential biomarkers for PAH monitoring and risk assessment.
abstract: To identify potential biomarkers for the monitoring and risk assessment of benzo[a]pyrene (BaP), the oxidative stress-related DNA damage and p53 modification were investigated in human hepatoma HepG2 cells. Benzo[a]pyrene exposure induced a decrease in the cell viability, but increased the antioxidant enzyme activity as well as the DNA and lipid damage. The p53 protein activation appeared to have been a downstream response to the benzo[a]pyrene-induced DNA damage, suggesting p53 plays important roles in the defense against benzo[a]pyrene-induced genotoxicity. The response of phosphorylated p53 may be more sensitive towards benzo[a]pyrene exposure than normal p53. Following DNA damage, the activation of p53 acts as a transcriptional regulator of several target genes, including, p21 protein; a gene that encodes the Cdk inhibitor and is induced by exposure to benzo[a]pyrene. The p53 mRNA level was increased after the treatment of cells with benzo[a]pyrene, as well as following the induction of p53 protein, suggesting the benzo[a]pyrene-stimulated p53 accumulation may also be transcriptionally induced. The overall results suggest that benzo[a]pyrene leads to serious DNA damage, which leads to the transcription of the p53 gene; that the subsequent p53 protein accumulation up-regulates the cellular p21 protein. Oxidative DNA damage and p53 accumulation seem to be related to benzo[a]pyrene toxicity; however, their potential as biomarkers in environmental monitoring and risk assessment needs to be validated in the context of their specificity and sensitivity.
authors.affiliation: Faculty of Environmental Engineering, College of Urban Study, University of Seoul, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Lee
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Yoon
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Chung
authors.forename: Jinhee
authors.initials: J
authors.lastname: Choi
mesh_terms: D001564:Benzo(a)pyrene / Q000032:analysis / Q000633:toxicity*; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D004249:DNA Damage / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D005434:Flow Cytometry; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008113:Liver Neoplasms / Q000378:metabolism*; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity*; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment
chemical_list: D014408:Biomarkers, Tumor; D004785:Environmental Pollutants; D011084:Polycyclic Aromatic Hydrocarbons; D016160:Retinoblastoma Protein; D001564:Benzo(a)pyrene; D002374:Catalase; D018844:Cyclin-Dependent Kinases; D015689:Oncogene Protein p21(ras)