title: Tumour-promoting activity of polycyclic aromatic hydrocarbons and their oxygenated or nitrated derivatives.
abstract: Various types of polycyclic aromatic compounds (PACs) in diesel exhaust particles are thought to contribute to carcinogenesis in mammals. Although the carcinogenicity, mutagenicity and tumour-initiating activity of these compounds have been evaluated, their tumour-promoting activity is unclear. In the present study, to determine the tumour-inducing activity of PACs, including previously known mutagenic compounds in atmospheric environments, a transformation assay for promoting activity mediated by the release of contact inhibition was conducted for six polycyclic aromatic hydrocarbons (PAHs), seven oxygenated PAHs (oxy-PAHs) and seven nitrated PAHs (nitro-PAHs) using mouse embryonic fibroblast cells transfected with the v-Ha-ras gene (Bhas 42 cells). Of these, two PAHs [benzo[k]fluoranthene (B[k]FA) and benzo[b]fluoranthene (B[b]FA)], one oxy-PAH [6H-benzo[cd]pyren-6-one (BPO)] and two nitro-PAHs (3-nitro-7H-benz[de]anthracen-7-one and 6-nitrochrysene) were found to exhibit particularly powerful tumour-promoting activity (≥10 foci following exposure to <100nM). In addition, clear mRNA expression of CYP1A1, which is associated with aryl hydrocarbon receptor (AhR)-mediated activation, was observed following the exposure of cells to two PAHs (B[k]FA and B[b]FA) and three oxy-PAHs (1,2-naphthoquinone, 11H-benzo[b]fluoren-11-one and BPO). Further, an HO-1 antioxidant response activation was observed following exposure to B[k]FA, B[b]FA and BPO, suggesting that the induction of tumour-promoting activity in these compounds is correlated with the dysfunction of signal transduction via AhR-mediated responses and/or oxidative stress responses.
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan, School of Nursing, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan and kmisaki@u-shizuoka-ken.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Misaki
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-Enya
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Yanagida
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000737:chemistry* / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry* / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics; D001335:Vehicle Emissions / Q000633:toxicity
chemical_list: D002273:Carcinogens; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D001335:Vehicle Emissions