title: Ah-receptor-independent stimulation of hepatoma 27 culture cell proliferation by polycyclic aromatic hydrocarbons.
abstract: The proliferative effect of some compounds that are aryl hydrocarbon (Ah) receptor ligands was studied on hepatoma 27 cells with absent expression of Ah receptor. Compounds of the polycyclic aromatic hydrocarbon (PAH) class benzo/a/pyrene, 3-methylcholanthrene, 7,12-dimethylbenz/a/anthracene, and benzo/e/pyrene as well as β-naphthoflavone (β-NF) and chlorinated hydrocarbon Aroclor 1254 were studied. It was found that carcinogenic PAH and β-NF stimulate cell proliferation both under conditions of standard serum content and in a medium with low serum content. More efficient stimulation of proliferation was observed in the case of low serum content. Aroclor 1254 and benzo/e/pyrene did not stimulate cell proliferation. Stimulation of proliferation was accompanied by activation of the ERK1/2-dependent MAP-kinase cascade. Benzo/a/pyrene caused a decrease in the number of cells in G1 phase of the cell cycle and increase in number of cells in G2/M phases under conditions of cell growth in media with low serum content. Carcinogenic PAH and β-NF activated transcription factor AP-1, and in this case activation was more pronounced in cells grown in medium with low serum content. A possible mechanism of activation of proliferation by an Ah receptor-independent pathway is discussed.
authors.affiliation: Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: M S
authors.initials: MS
authors.lastname: Volkov
authors.forename: N A
authors.initials: NA
authors.lastname: Bolotina
authors.forename: V A
authors.initials: VA
authors.lastname: Evteev
authors.forename: V A
authors.initials: VA
authors.lastname: Koblyakov
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D059565:G2 Phase Cell Cycle Checkpoints; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D018808:Transcription Factor AP-1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases