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.
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.
Park
Sun-Young
SY
Faculty of Environmental Engineering, College of Urban Study, University of Seoul, Republic of Korea.
Lee
Sun-Mi
SM
Ye
Sang-Kyu
SK
Yoon
Sun-Hee
SH
Chung
Myung-Hee
MH
Choi
Jinhee
J
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
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)