The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells

Andrysík, Zdeněk; Vondráček, Jan; Machala, Miroslav; Krčmář, Pavel; Šindlerová, Lenka; Kranz, Anne; Weiss, Carsten; Faust, Dagmar; Kozubı́k, Alois; Dietrich, Cornelia

doi:10.1016/j.mrfmmm.2006.10.004

Cited by 76 publications

(54 citation statements)

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“…Besides direct inhibition of CYP enzymes involved in metabolic activation, PAH mixtures have been shown of being able to target the expression of regulatory proteins involved in metabolism, DNA repair, cell cycle regulation, cellular migration and adhesion, thus altering the cell's ability to maintain its genomic integrity and growth control [27,[59][60][61][62][63]. In the present study we determined gene expression changes in tumor tissue developed in mice upon treatment with BP or DBP in the absence or presence of SRM 1975 (Fig.…”

Section: Discussionmentioning

confidence: 99%

The influence of diesel exhaust on polycyclic aromatic hydrocarbon-induced DNA damage, gene expression, and tumor initiation in Sencar mice in vivo

et al. 2008

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The carcinogenic effects of individual polycyclic aromatic hydrocarbons (PAH) are well established. However, their potency within an environmental complex mixture is uncertain. We evaluated the influence of diesel exhaust particulate matter on PAH-induced cytochrome P450 (CYP) activity, PAH-DNA adduct formation, expression of certain candidate genes and the frequency of tumor initiation in the two-stage Sencar mouse model. To this end, we monitored the effects of treatment of mice with diesel exhaust, benzo[a]pyrene (BP), dibenzo [a,l]pyrene (DBP), or a combination of diesel exhaust with either carcinogenic PAH. The applied diesel particulate matter (SRM 1975 ) altered the tumor initiating potency of DBP: a statistically significant decrease in overall tumor and carcinoma burden was observed following 25 weeks of promotion with 12-Otetradecanoylphorbol-13-acetate (TPA), compared with DBP exposure alone. From those mice that were treated at the beginning of the observation period with 2 nmol DBP all survivors developed tumors (9 out of 9 animals, 100%). Among all tumors counted at the end, 9 carcinomas were detected and an overall tumor incidence of 2.6 tumors per tumor-bearing animal (TBA) was determined. By contrast, co-treatment of DBP with 50 mg SRM 1975 led to a tumor rate of only 66% (19 out of 29 animals), occurrence of only 3 carcinomas in 29 animals and an overall rate of 2.1 tumors per TBA (P = 0.04). In contrast to the results with DBP, the tumor incidence induced by 200 nmol BP was Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. found slightly increased when co-treatment with SRM 1975 occurred (71% vs. 85% after 25 weeks). Despite this difference in tumor incidence, the numbers of carcinomas and tumors per TBA did not differ statistically significant between both treatment groups possibly due to the small size of the BP treatment group. Since bioactivation of DBP, but not BP, predominantly depends on CYP1B1 enzyme activity, SRM 1975 affected PAH-induced carcinogenesis in an antagonistic manner when CYP1B1-mediated bioactivation was required. The explanation most likely lies in the much stronger inhibitory effects of certain PAHs present in diesel exhaust on CYP1B1 compared to CYP1A1. In the present study we also found molecular markers such as highly elevated AKR1C21 and TNFRSF21 gene expression levels in tumor tissue derived from animals co-treated with SRM 1975 plus DBP. Therefore we validate microarray data as a source to uncover transcriptional signatures that may provide insights into molecular pathways affected following exposure to environmental...

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Section: Discussionmentioning

confidence: 99%

The influence of diesel exhaust on polycyclic aromatic hydrocarbon-induced DNA damage, gene expression, and tumor initiation in Sencar mice in vivo

et al. 2008

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“…Andrew et al (2006) found that BaP may induce human breast cancer by analysis of proliferation of mammary cells exposed to BaP. Andrysik et al (2007) reported that BaP could lead to enhanced cell proliferation and mutations in rat liver epithelial cells. The value for the oral carcinogenicity unit risk (CUR) of BaP is 0.0029 lg/l (US-EPA 2008).…”

Section: Resultsmentioning

confidence: 99%

Degradation of benzo(a)pyrene in Yangtze River source water with functional strains

Zhang

et al. 2009

Ecotoxicology

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Degradation of benzo(a)pyrene (BaP) existing in the Yangtze River, used as source water for Nanjing City, China, was investigated with functional strains. The removal rates of BaP were 37.5, 20.8 and 70.8% for the three strains of the native bacterium NJ, and the two functional strains of Xhhh and Fhhh, respectively. The Fhhh specific degradation rate of BaP was 3.02 x 10(-6) day(-1), which was 1.9-fold of the rate with NJ and 3.7-fold of the rate with Xhhh. The concentrations of BaP in the source water, tap water and Fhhh reactor effluent were 8.3-, 7.6-, and 2.4-fold of that of the oral carcinogenicity unit risk. The results suggest that the functional strain Fhhh could be used for the reduction of BaP concentrations in source water and hence reduction of carcinogenic risk.

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“…It has been described that the checkpoints cannot repair the DNA at high levels of cell injury, and as a result, the division phases cannot be completed, leading to cell apoptosis to avoid the division of cells with DNA damage (Binkov a et al, 2000;Andrysík et al, 2007;Hrub a et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that PAHs induce problems in DNA replication and interrupt the division cycle in the S-phase (DNA synthesis) (e.g. Andrysík et al, 2007, Binkov a et al, 2000. Damage of DNA is also described for prokaryotic cells that expressed genes involved in DNA reparation when exposed to PAHs (Gu et al, 2000;Kim et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

PAHs reduce DNA synthesis and delay cell division in the widespread primary producer Prochlorococcus

Cerezo¹,

Agustı́²

2015

Environmental Pollution

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The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells

Cited by 76 publications

References 50 publications

The influence of diesel exhaust on polycyclic aromatic hydrocarbon-induced DNA damage, gene expression, and tumor initiation in Sencar mice in vivo

The influence of diesel exhaust on polycyclic aromatic hydrocarbon-induced DNA damage, gene expression, and tumor initiation in Sencar mice in vivo

Degradation of benzo(a)pyrene in Yangtze River source water with functional strains

PAHs reduce DNA synthesis and delay cell division in the widespread primary producer Prochlorococcus

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