Dibenzanthracenes and benzochrysenes elicit both genotoxic and nongenotoxic events in rat liver 'stem-like' cells
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17287060
DOI
10.1016/j.tox.2006.12.024
PII: S0300-483X(07)00016-9
Knihovny.cz E-resources
- MeSH
- DNA Adducts metabolism MeSH
- Enzyme Activation MeSH
- Apoptosis drug effects MeSH
- Aryl Hydrocarbon Hydroxylases biosynthesis genetics metabolism MeSH
- Benz(a)Anthracenes toxicity MeSH
- Chrysenes toxicity MeSH
- Cytochrome P-450 CYP1A1 biosynthesis genetics metabolism MeSH
- Cytochrome P-450 CYP1B1 MeSH
- Hydroxysteroid Dehydrogenases biosynthesis genetics metabolism MeSH
- Liver cytology drug effects enzymology metabolism MeSH
- Carcinogens toxicity MeSH
- Rats MeSH
- RNA, Messenger biosynthesis genetics MeSH
- Gap Junctions drug effects MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Cell Proliferation drug effects MeSH
- Receptors, Aryl Hydrocarbon metabolism MeSH
- Environmental Exposure MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3-hydroxysteroid dihydrodiol dehydrogenase MeSH Browser
- DNA Adducts MeSH
- Aryl Hydrocarbon Hydroxylases MeSH
- Benz(a)Anthracenes MeSH
- Chrysenes MeSH
- Cyp1b1 protein, rat MeSH Browser
- Cytochrome P-450 CYP1A1 MeSH
- Cytochrome P-450 CYP1B1 MeSH
- dibenzanthracenes MeSH Browser
- Hydroxysteroid Dehydrogenases MeSH
- Carcinogens MeSH
- RNA, Messenger MeSH
- Receptors, Aryl Hydrocarbon MeSH
Polycyclic aromatic hydrocarbons (PAHs) with molecular weight 278 are a group of PAHs that are mostly not covered by the current monitoring programs, despite their relative abundance in environmental samples and possible carcinogenicity. Although benzo[g]chrysene (BgChry) and dibenz[a,h]anthracene (DBahA) have been for a long time studied as genotoxic, tumour-initiating compounds, little is known about the potential tumour-promoting effects of this group of PAHs. In the present study, we investigated their impact on activation of the aryl hydrocarbon receptor (AhR), induction of enzymes involved in metabolic activation of PAHs, disruption of cell cycle control in confluent cell population and inhibition of gap junctional intercellular communication (GJIC), using the rat liver epithelial cell line WB-F344 as a model of liver progenitor cells. We found that BgChry was the weakest inducer of the AhR-mediated activity, while relative potencies of benzo[b]chrysene (BbChry) and benzo[c]chrysene (BcChry) were comparable to the previously reported values for dibenzanthracenes. All compounds increased expression of cytochromes P450 1A1 and 1B1, and aldo-keto reductase 1C9. BgChry was found to induce high amounts of DNA adducts, which corresponded with induction of p53 phosphorylation at Ser15, apoptosis and accumulation of cells in S-phase of cell cycle, leading to a decrease in cell numbers. All other compounds were found to stimulate cell proliferation in contact-inhibited WB-F344 cells in a dose-dependent manner. We found that only BgChry, and to a lesser extent also BcChry, inhibited GJIC at high concentrations. Taken together, dibenzanthracenes and benzochrysenes, with exception of BgChry, seem to act primarily through deregulation of cell proliferation in liver epithelial cells, which is related to their relatively high AhR-mediated activity. The disruption of cell cycle control might contribute to their carcinogenic effects, as well as to carcinogenicity of complex environmental mixtures containing high levels of PAHs with molecular weight 278.
References provided by Crossref.org
Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing