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.

Degenerative and Regenerative Actin Cytoskeleton Rearrangements, Cell Death, and Paradoxical Proliferation in the Gills of Pearl Gourami (Trichogaster leerii) Exposed to Suspended Soot Microparticles

“…The Ah-receptor-mediated effects are fairly broad and include detoxification, cell proliferation, and migration [127]. However, benz[a]pyrene was shown to activate cell proliferation [124] via an Ah-receptor-independent pathway [128]. In addition to the activation of the proliferation of gill epithelial cells by soot components, this process can also be induced by apoptosis (the so-called apoptosis-induced compensatory proliferation) [129].…”

The polyaromatic hydrocarbon β-naphthoflavone alters binding of YY1, Sp1, and Sp3 transcription factors to the Dp71 promoter in hepatic cells

“…The synthetic polyaromatic hydrocarbon, β-naphthoflavone (β-NF), has been extensively used to analyze the effect of xenobiotics on a large number of genes involved in metabolic and adaptive processes (20,21). In previous studies, we showed that both in vitro and in vivo expression of Dp71 in hepatic cells is repressed by β-NF (22).…”

Sub-acute exposure effect of selected polycyclic aromatic hydrocarbons on protein levels of epigenetic modifiers in non-cancerous hepatic model

“…These compounds are classical substrates and inducers of cytochrome P450 enzymes (CYP), particularly the isoforms CYP1B1 and CYP1A1 [15], which in turn generate highly reactive metabolites, which react with proteins and DNA, leading to mutagenesis and carcinogenesis [16]. In addition to these effects, they are estrogenic compounds, modulators of cell cycle, proliferation and even modulators of angiogenesis [17][18][19][20].…”