Methylated chrysenes (MeChry) are important cigarette smoke constituents and 5-MeChry has been listed as possibly carcinogenic to humans. Although a major attention has been in past paid especially to mutagenic, tumor-initiating effects of MeChry, little is known about toxic effects of MeChry related to tumor promotion. As the position of methyl group has been repeatedly observed to determine genotoxic effects of MeChry, we examined both genotoxic and nongenotoxic effects of MeChry, using rat liver cell lines as experimental models. All six MeChry were relatively efficient aryl hydrocarbon receptor (AhR) agonists, with 3- and 6-MeChry being the most potent inducers of the AhR-mediated reporter gene activity. All six compounds disrupted contact inhibition in rat liver epithelial WB-F344 cells, a process previously reported to be AhR-dependent, suggesting that MeChry may interfere with cell cycle control in an AhR-dependent manner. In contrast, only 5- and 6-MeChry were found to acutely inhibit gap junctional intercellular communication (GJIC), another parameter correlating with tumor promoting effects of xenobiotics. Both 5- and 6-MeChry were efficient inducers of mRNA expression of enzymes involved in metabolic activation of polycyclic aromatic hydrocarbons, including cytochromes P450 1A1/1B1 and aldo-keto reductase 1C9. However, only 5-MeChry, and not 6-MeChry, induced significant formation of DNA adducts in rat liver epithelial cells, which corresponded with its ability to induce high accumulation of cells in S-phase. On the other hand, 5-MeChry induced neither apoptosis related to DNA damage nor phosphorylation of p53 tumor suppressor. Taken together, our results suggest that methyl group position may affect both genotoxic and nongenotoxic effects of MeChry, such as formation of DNA adducts and inhibition of GJIC. All MeChry showed a potency to disrupt cell proliferation control, while 5-MeChry was a single compound inducing DNA damage, disruption of cell cycle control and inhibition of GJIC in rat liver cells.

• MeSH
• adukty DNA metabolismus   MeSH
• buněčný cyklus účinky léků   MeSH
• chryseny toxicita   MeSH
• enzymová indukce účinky léků   MeSH
• epitelové buňky účinky léků   MeSH
• játra účinky léků   MeSH
• karcinogeny toxicita   MeSH
• krysa rodu Rattus MeSH
• mezerový spoj účinky léků   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• receptory aromatických uhlovodíků fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 5-methylchrysene MeSH Prohlížeč
• 6-methylchrysene MeSH Prohlížeč
• adukty DNA MeSH
• chryseny MeSH
• karcinogeny MeSH
• receptory aromatických uhlovodíků 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.

• MeSH
• adukty DNA metabolismus   MeSH
• aktivace enzymů MeSH
• apoptóza účinky léků   MeSH
• aromatické hydroxylasy biosyntéza   genetika   metabolismus   MeSH
• benz(a)anthraceny toxicita   MeSH
• chryseny toxicita   MeSH
• cytochrom P-450 CYP1A1 biosyntéza   genetika   metabolismus   MeSH
• cytochrom P450 CYP1B1 MeSH
• hydroxysteroiddehydrogenasy biosyntéza   genetika   metabolismus   MeSH
• játra cytologie   účinky léků   enzymologie   metabolismus   MeSH
• karcinogeny toxicita   MeSH
• krysa rodu Rattus MeSH
• messenger RNA biosyntéza   genetika   MeSH
• mezerový spoj účinky léků   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proliferace buněk účinky léků   MeSH
• receptory aromatických uhlovodíků metabolismus   MeSH
• vystavení vlivu životního prostředí MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-hydroxysteroid dihydrodiol dehydrogenase MeSH Prohlížeč
• adukty DNA MeSH
• aromatické hydroxylasy MeSH
• benz(a)anthraceny MeSH
• chryseny MeSH
• Cyp1b1 protein, rat MeSH Prohlížeč
• cytochrom P-450 CYP1A1 MeSH
• cytochrom P450 CYP1B1 MeSH
• dibenzanthracenes MeSH Prohlížeč
• hydroxysteroiddehydrogenasy MeSH
• karcinogeny MeSH
• messenger RNA MeSH
• receptory aromatických uhlovodíků MeSH

Polycyclic aromatic hydrocarbons have shown to be an important class of environmental and occupational carcinogens. By balancing the carcinogenic potential PAH were found to predominantly contribute to the biological activity of environmental matter such as vehicle exhaust, used motor oil, and hard-coal combustion effluents. Due to the individual ratio of toxifying and detoxifying processes PAH-exposure measurements are not appropriate to be used for risk assessment without any further information on their metabolic fate. Accordingly, metabolite profiles of phenanthrene, pyrene, chrysene, benz(a)anthracene and fluoranthene have been recorded in both tar-pitch exposed Wistar rats and coke plant workers. The results show that metabolite profiles are invariant individual parameters which, however, vary from one individual to another. Significant differences with regard to the ratio of k-region and non-k-region hydroxylation of phenanthrene have been observed in a greater number of coke plant workers. This ratio might be helpful for risk assessment studies since it reflects the various cytochrome P450-dependent monooxygenase isoforms participating in the metabolism of PAH. Studies of this kind can only be carried out with substrates possessing several nonequivalent double bonds (phenanthrene, chrysene) whereas pyrene--commonly used for biomonitoring--does not satisfy this condition. The excretion rate (excretion versus exposure) seems to be an individual parameter.

• MeSH
• benz(a)anthraceny metabolismus   MeSH
• benzopyren metabolismus   MeSH
• chemický průmysl * MeSH
• chryseny metabolismus   MeSH
• feces chemie   MeSH
• fenantreny metabolismus   MeSH
• hodnocení rizik MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• metylace MeSH
• monitorování životního prostředí MeSH
• polycyklické aromatické uhlovodíky metabolismus   moč   MeSH
• potkani Wistar MeSH
• pracovní expozice * MeSH
• vystavení vlivu životního prostředí * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benz(a)anthracene MeSH Prohlížeč
• benz(a)anthraceny MeSH
• benzopyren MeSH
• chrysene MeSH Prohlížeč
• chryseny MeSH
• fenantreny MeSH
• phenanthrene MeSH Prohlížeč
• polycyklické aromatické uhlovodíky MeSH

The interaction of gaseous NO2 with solid carrier-adsorbed polycyclic aromatic hydrocarbons was studied under laboratory conditions with a specific attention to factors that might possibly influence this reaction, such as type of carrier lighting conditions, NO2 concentration, exposure time, and temperature. At the NO2 concentration of 1.33 ppm there were detected the following nitro derivatives: nitroanthracene, nitropyrene, nitrochrysene, two mononitro derivatives of benzo/a/pyrene, and dinitrobenzo/a/pyrene. The experimental data suggest that the formation of nitroaromates in atmospheric environment is to be expected, provided that there are present, besides polycyclic aromatic hydrocarbons and nitrogen oxides, also suitable types of sorbents, such as silica gel or fly ash.

• MeSH
• anthraceny * MeSH
• benzopyreny MeSH
• chemické jevy MeSH
• chemie MeSH
• chryseny * MeSH
• fenantreny * MeSH
• látky znečišťující vzduch * MeSH
• oxid dusičitý * MeSH
• oxid hlinitý MeSH
• oxid křemičitý MeSH
• pyreny * MeSH
• světlo MeSH
• teplota MeSH
• uhlík MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anthraceny * MeSH
• benzopyreny MeSH
• chryseny * MeSH
• fenantreny * MeSH
• látky znečišťující vzduch * MeSH
• oxid dusičitý * MeSH
• oxid hlinitý MeSH
• oxid křemičitý MeSH
• pyreny * MeSH
• uhlík MeSH