title: Two-stage exposure of Syrian-hamster-embryo cells to environmental carcinogens: superinduction of ornithine decarboxylase correlates with increase of morphological-transformation frequency.
abstract: As part of environmental toxicology, it is important to assess both the carcinogenic potential of xenobiotics and their mode of action on target cells. Since dysregulation of ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, is considered as an early and essential component in the process of multistage carcinogenesis, we have studied the mode of ODC induction in Syrian-hamster-embryo(SHE) cells stage-exposed to carcinogens and to non-carcinogens. One-stage (5 hr) treatment of SHE cells with 50 microM clofibrate (CLF), a non-genotoxic carcinogen, or with 0.4 microM benzo(a)pyrene (BaP), a genotoxic carcinogen, slightly decreased basal ODC activity. Using the 2-stage exposure, 1 hr to carcinogen, then replacement by TPA for 5 hr, the ODC activity was higher than that obtained with TPA alone. This ODC superinduction was not observed when SHE cells were similarly pre-treated with non-carcinogenic compounds. Several environmental chemicals, pesticides, solvents, oxidizers and drugs were investigated with this SHE cell model. With one-stage exposure, some xenobiotics decreased basal ODC activity, while for others ODC changes were not noticeable. With 2-stage exposure (chemical followed by TPA), all carcinogens amplified the TPA-inducing effect, resulting in ODC superinduction. Comparative studies of the action of carcinogens and of non-carcinogens, using 2-stage exposure protocols, clearly show a close relationship between ODC induction rate and morphological transformation frequency.
authors.affiliation: Laboratory of Cellular and Molecular Pharmacology, CNRS-URA 1218, Chatenay-Malabry, France.
authors.forename: S
authors.initials: S
authors.lastname: Dhalluin
authors.forename: Z
authors.initials: Z
authors.lastname: Elias
authors.forename: V
authors.initials: V
authors.lastname: Cruciani
authors.forename: H
authors.initials: H
authors.lastname: Bessi
authors.forename: O
authors.initials: O
authors.lastname: Poirot
authors.forename: C
authors.initials: C
authors.lastname: Rast
authors.forename: L
authors.initials: L
authors.lastname: Gate
authors.forename: N
authors.initials: N
authors.lastname: Pages
authors.forename: H
authors.initials: H
authors.lastname: Tapiero
authors.forename: P
authors.initials: P
authors.lastname: Vasseur
authors.forename: G
authors.initials: G
authors.lastname: Nguyen-Ba
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage; D002273:Carcinogens / Q000008:administration & dosage*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D002994:Clofibrate / Q000008:administration & dosage; D006224:Cricetinae; D004334:Drug Administration Schedule; D004790:Enzyme Induction / Q000187:drug effects; D008647:Mesocricetus / Q000196:embryology; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage
chemical_list: D002273:Carcinogens; D001564:Benzo(a)pyrene; D009955:Ornithine Decarboxylase; D002994:Clofibrate; D013755:Tetradecanoylphorbol Acetate