Induction of cell death, DNA strand breaks, and cell cycle arrest in DU145 human prostate carcinoma cell line by benzo[a]pyrene and benzo[a]pyrene-7,8-diol-9,10-epoxide.

Onyinye Nwagbara,Richard Gragg,Alicia Tucker,Ronald Thomas,Selina Darling-Reed,Michael Abazinge,Cynthia Harris

doi:10.3390/ijerph2007010002

Abstract

Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a major environmental pollutant. In this study, the effects of this carcinogen/mutagen and one of its metabolites, benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), on human prostate carcinoma cell line DU145, were examined. Cell viability, DNA damage, and cell cycle progression were evaluated as toxic end-points. We have shown that B[a]P and BPDE inhibited cell viability following 48 hr of exposure. Furthermore, comet assay analyses revealed that both B[a]P and BPDE induced DNA strand breaks in a concentration-dependent fashion. Flow cytometric analyses showed that about 70% of DU145 cells were arrested by B[a]P at the G1 phase, while about 76% were arrested at G1 phase by BPDE. These data reveal that B[a]P and BPDE are cytotoxic and genotoxic to DU145 prostate cancer cells.

Highlights

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental and occupational pollutants formed from the combustion of organic compounds
Our results demonstrated that varying concentrations of B[a]P and BPDE induced cell death, DNA strand breaks and cell cycle arrest in a dose-dependent manner
DU145 cells at density of 106 cells/ml were treated with DMSO (0.1%, vehicle control), B[a]P (5, 20, and 50 μM ) and BPDE (1, 5, and 10 μM) and incubated for 48 hours

Summary

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental and occupational pollutants formed from the combustion of organic compounds. Our results demonstrated that varying concentrations of B[a]P and BPDE induced cell death, DNA strand breaks and cell cycle arrest in a dose-dependent manner. The effects of B[a]P and BPDE on cell viability of DU145 was determined using the MTT assay. The cells were incubated with B[a]P at concentrations of 5.0, 20, and 50 μM and with BPDE at concentrations of 1.0, 5.0, and 10.0 μM, and DMSO (0.1%) for 48 hours.

Results

Conclusion