title: Genotoxic and cytotoxic effects of the environmental pollutant 3-nitrobenzanthrone on bladder cancer cells.
abstract: 3-Nitrobenzanthrone (3-NBA), a potential human carcinogen, is present in diesel exhaust. The main metabolite of 3-NBA, 3-aminobenzanthrone, was detected in urine of miners occupationally exposed to diesel emissions. Environmental and occupational factors play an important role in development of bladder cancer (BC), one of the most frequent malignancies. It is expected that exposure of urothelium to 3-NBA and its metabolites may induce BC initiation and/or progression. To test this hypothesis, we studied geno- and cytotoxicity of 3-NBA using an in vitro BC model. 3-NBA induced higher levels of DNA adducts, reactive oxygen species and DNA breaks in aggressive T24 cells than in more differentiated RT4 cells. To understand the nature of this difference we examined the role of several enzymes that were identified as 3-NBA bio activators. However, the difference in DNA adduct formation cannot be directly linked to the different activity of any of the examined enzymes. Conversely, the difference of tested cell lines in p53 status can partly explain the distinct levels of 3-NBA-DNA adducts and DNA damage induced by 3-NBA. Therefore, we assume that more aggressive T24 cells are more predisposed for DNA adduct formation, DNA damage and, possibly, mutations and as a result further tumorigenesis.
authors.affiliation: Department of Urology, SUNY at Stony Brook, 11794, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Reshetnikova
authors.affiliation: Department of Pharmacological Sciences, SUNY at Stony Brook, 11794, USA.
authors.forename: Viktoriya S
authors.initials: VS
authors.lastname: Sidorenko
authors.affiliation: Department of Urology, SUNY at Stony Brook, 11794, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Whyard
authors.affiliation: Department of Pharmacological Sciences, SUNY at Stony Brook, 11794, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lukin
authors.affiliation: Department of Urology, SUNY at Stony Brook, 11794, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Waltzer
authors.affiliation: Department of Applied Chemistry, Kanagawa Institute of Technology, 1030 Shimo-ogino, Atsugi, Kanagawa 243-0292, Japan.
authors.forename: Takeji
authors.initials: T
authors.lastname: Takamura-Enye
authors.affiliation: Department of Urology, SUNY at Stony Brook, 11794, USA. Electronic address: victor.romanov@stonybrookmedicine.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Romanov
mesh_terms: D001551:Benz(a)Anthracenes / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D001551:Benz(a)Anthracenes; D018736:DNA Adducts; D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D003577:Cytochrome P-450 Enzyme System; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C117220:3-nitrobenzanthrone
keywords: 3-Nitrobenzanthrone; Bladder cancer; Molecular carcinogenesis