Benzo[a]pyrene induced p53-mediated cell cycle arrest, DNA repair, and apoptosis pathways in Chinese rare minnow (<i>Gobiocypris rarus</i>)

Yuan, Lilai; Lv, Biping; Zha, Jinmiao; Wang, Zijian

doi:10.1002/tox.22298

Cited by 23 publications

(8 citation statements)

References 57 publications

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“…Each sample was run in triplicate. The primers in this study are shown in Table S1 (Yuan et al, 2016). The PCR efficiencies ranged from 93.2% to 103.0% in the present study.…”

Section: Rt-qpcrmentioning

confidence: 64%

Benzo(a)pyrene-induced a mitochondria-independent apoptosis of liver in juvenile Chinese rare minnows (Gobiocypris rarus)

Zha

Hong

Rao

et al. 2017

Environmental Pollution

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To examine the effects of BaP on tissue apoptosis, laboratory studies were conducted using juvenile Chinese rare minnows (Gobiocypris rarus) exposed to 1, 5, 20, and 80 μg/L of BaP for 28 days. The post-treatment pathological findings in the liver were associated with hepatocyte swelling, karyopyknosis, and karyorrhexis. Moreover, an increase in the goblet cells in the intestine, epithelial hyperplasia of the gills and fusion of gill lamellae were observed. Significant increases in hepatocyte apoptosis using the TUNEL stain were observed in the liver tissue but not in the intestine and gills. In addition, BaP exposure significantly up-regulated the mRNA levels of cyp1a1, p53, bax, bcl-2, and caspase-9 in the liver following the 5, 20, and 80 μg/L treatments, whereas the apaf-1 was significantly down-regulated following all treatments. Moreover, the activities of caspase 3 and caspase 8 were markedly elevated, whereas the protein expression levels of Apaf-1 were down-regulated following the 20 and 80 μg/L treatments. Taken together, our results suggested that BaP strongly induces tissue-specific apoptosis in vivo, leading to significant pathological changes. The responsiveness of apoptotic-related genes demonstrates that BaP induced apoptosis in the liver may be through a mitochondria-independent pathway.

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“…Each sample was run in triplicate. The primers in this study are shown in Table S1 (Yuan et al, 2016). The PCR efficiencies ranged from 93.2% to 103.0% in the present study.…”

Section: Rt-qpcrmentioning

confidence: 64%

Benzo(a)pyrene-induced a mitochondria-independent apoptosis of liver in juvenile Chinese rare minnows (Gobiocypris rarus)

Zha

Hong

Rao

et al. 2017

Environmental Pollution

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“…They do not provide insights into the underlying molecular mechanisms responsible for toxicity. For that purpose and considering that other studies have reported that PAHs and HPAHs could induce oxidative stress and apoptosis , complementary methods were used in the present study to characterize these effects.…”

Section: Resultsmentioning

confidence: 99%

Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line

Morgado¹,

José²,

Wanke

et al. 2017

Enviro Toxic and Chemistry

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Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effects of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr), and 3 halogenated derivatives of these compounds (1-chloropyrene, 1-bromopyrene [1-BrPyr], and 7-chlorobenzo[a]anthracene [7-ClBaA]) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72 h, except for multiple dose exposure to BaA and 7-ClBaA (1 μM/d for 4 d) and single exposure to 10 μM BaA. Furthermore, selective mitochondrial and lysosomal toxicity was observed for Pyr and BaA series, respectively. To understand the underlying molecular mechanisms responsible for this effect, reactive oxygen species production, mitochondrial membrane depolarization, lysosomal pH, DNA fragmentation, and early and late apoptosis mediators were evaluated after exposure to single doses of the compounds. All compounds were able to trigger oxidative stress after 24 h as measured by catalase activity, and a good correlation was found between mitochondrial membrane depolarization, lysosomal pH increase, and MTT and neutral red assays. Evaluation of cell death mediators showed that caspase-3/7, but not annexin-V, pathways were involved in toxicity triggered by the studied compounds. The integration of all results showed that 1-BrPyr and BaA have a higher toxicity potential. Environ Toxicol Chem 2017;36:3404-3414. © 2017 SETAC.

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“…Several signaling pathways have been shown to be activated by the presence of reactive oxygen species, a by-product of cellular activation by BaP [ 111 , 143 , 144 , 145 , 146 , 147 , 148 , 149 ]. The PI3K-Akt signaling pathway is one of the most important pathways involved in the proliferation and survival of cells [ 150 , 151 , 152 ].…”

Section: Discussionmentioning

confidence: 99%

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

et al. 2018

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Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might occur. Method: We report here on the effects of benzo-α-pyrene on esophageal cancer cells in vitro, alone, or in combination with chemotherapeutic drugs cisplatin, 5-flurouracil, or paclitaxel. As the study endpoints, we employed expression of proteins involved in cell proliferation, drug metabolism, apoptosis, cell cycle analysis, colony formation, migration, and signaling cascades in the WHCO1 esophageal cancer cell line after 24 h of treatment. Results: Benzo-α-pyrene had no significant effect on WHCO1 cancer cell proliferation but reversed the effect of chemotherapeutic drugs by reducing drug-induced cell death and apoptosis by 30–40% compared to drug-treated cells. The three drugs significantly reduced WHCO1 cell migration by 40–50% compared to control and BaP-treated cells. Combined exposure to drugs was associated with significantly increased apoptosis and reduced colony formation. Evaluation of survival signaling cascades showed that although the MEK-ERK and Akt pathways were activated in the presence of drugs, BaP was a stronger activator of the MEK-ERK and Akt pathways than the drugs. Conclusion: The present study suggest that BaP can reverse the effects of drugs on cancer cells via the activation of survival signaling pathways and upregulation of anti-apoptotic proteins such as Bcl-2 and Bcl-xL. Our data show that BaP contribute to the development of chemoresistant cancer cells.

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Benzo[a]pyrene induced p53-mediated cell cycle arrest, DNA repair, and apoptosis pathways in Chinese rare minnow (Gobiocypris rarus)

Cited by 23 publications

References 57 publications

Benzo(a)pyrene-induced a mitochondria-independent apoptosis of liver in juvenile Chinese rare minnows (Gobiocypris rarus)

Benzo(a)pyrene-induced a mitochondria-independent apoptosis of liver in juvenile Chinese rare minnows (Gobiocypris rarus)

Integration of cellular and molecular endpoints to assess the toxicity of polycyclic aromatic hydrocarbons in HepG2 cell line

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

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