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.
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.
Nwagbara
Onyinye
O
Environmental Sciences Institute, Florida A&M University, Tallahassee, FL 32307, USA. o.franklin.nwagbara@dep.state.fl.us
Darling-Reed
Selina F
SF
Tucker
Alicia
A
Harris
Cynthia
C
Abazinge
Michael
M
Thomas
Ronald D
RD
Gragg
Richard D
RD
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D002277:Carcinoma / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053960:DNA Breaks / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D018675:Toxicity Tests
D002273:Carcinogens; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide