Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells
Abstract
1. Introduction
2. Results
2.1. Phthalates
2.2. Liver GJIC between Oval Cells in Response to Phthalates
2.3. Viability of Liver Oval Cells in Response to Phthalates
2.4. MAPK-Erk1/2 Pathway in Liver Oval Cells in Response to Phthalates
2.5. Expression of Peroxisome Proliferator-Activated Receptors (Ppar) in Rat Liver Oval Cells WB-F344
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Cell Culture and Experimental Set-up
4.3. Cell Viability Assay
4.4. GJIC Assay
4.5. Western Blot
4.6. Reverse Transcription-Polymerase Chain Reaction (RT-PCR)
4.7. Data and Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
BBP | Benzyl butyl phthalate |
CaMgPBS | Calcium- and magnesium-supplemented PBS |
CFDA-AM | 5-Carboxyfluorescein diacetate, acetoxymethyl ester |
DAP | Diallyl phthalate |
DBP | Dibutyl phthalate |
DCHP | Dicyclohexyl phthalate |
DDP | Didecyl phthalate |
DEHP | Di-(2-etylhexyl) phthalate |
DEP | Diethyl phthalate |
DHpP | Diheptyl phthalate |
DIBP | Diisobutyl phthalate |
DIDP | Diisodecyl phthalate |
DIHpP | Diisoheptyl phthalate |
DILI | Drug-induced liver injury |
DINP | Diisononyl phthalate |
DIPrP | Diisopropyl phthalate |
DMP | Dimethyl phthalate |
DOP | Dioctyl phthalate |
DPeP | Dipentyl phthalate |
DPhP | Diphenyl phthalate |
DPrP | Dipropyl phthalate |
GJIC | Gap junctional intercellular communication |
LSPCs | Liver stem and progenitor cells |
MAPK | Mitogen-activated protein kinases |
MBP | Monobutyl phthalate |
MEHP | Mono(2-ethylhexyl) phthalate |
MINP | Monoisononyl phthalate |
MMP | Monomethyl phthalate |
MW | Molecular weight |
NRU | Neutral red uptake |
PPAR | Peroxisome proliferator-activated receptor |
PBS | Phosphate buffered saline |
SLDT | Scalpel load dye transfer |
TPA | 12-O-tetradecanoylphorbol 13-acetate |
References
- Schettler, T. Human exposure to phthalates via consumer products. Int. J. 2006, 29, 134–135. [Google Scholar] [CrossRef] [PubMed]
- Horn, O.; Nalli, S.; Cooper, D.; Nicell, J. Plasticizer metabolites in the environment. Water Res. 2004, 38, 3693–3698. [Google Scholar] [CrossRef]
- Przybylińska, P.A.; Wyszkowski, M. Environmental contamination with phthalates and its impact on living organisms. Ecol. Chem. Eng. S 2016, 23, 347–356. [Google Scholar] [CrossRef]
- Huang, P.C.; Tien, C.J.; Sun, Y.M.; Hsieh, C.Y.; Lee, C.C. Occurrence of phthalates in sediment and biota: Relationship to aquatic factors and the biota-sediment accumulation factor. Chemosphere 2008, 73, 539–544. [Google Scholar] [CrossRef] [PubMed]
- Rowdhwal, S.S.S.; Chen, J. Toxic effects of di-2-ethylhexyl phthalate: An overview. Biomed Res. Int. 2018, 2018, 1750368. [Google Scholar] [CrossRef] [PubMed]
- Heudorf, U.; Mersch-Sundermann, V.; Angerer, J. Phthalates: Toxicology and exposure. Int. J. Hyg. Environ. Health 2007, 210, 623–634. [Google Scholar] [CrossRef]
- Ashworth, M.J.; Chappell, A.; Ashmore, E.; Fowles, J. Analysis and assessment of exposure to selected phthalates found in children’s toys in Christchurch, New Zealand. Int. J. Environ. Res. Public Health 2018, 15, 200. [Google Scholar] [CrossRef]
- Larsson, K.; Lindh, C.H.; Jonsson, B.A.; Giovanoulis, G.; Bibi, M.; Bottai, M.; Bergstrom, A.; Berglund, M. Phthalates, non-phthalate plasticizers and bisphenols in Swedish preschool dust in relation to children’s exposure. Environ. Int. 2017, 102, 114–124. [Google Scholar] [CrossRef]
- Latini, G. Monitoring phthalate exposure in humans. Clin. Chim. Acta 2005, 361, 20–29. [Google Scholar] [CrossRef]
- Ito, Y.; Yamanoshita, O.; Asaeda, N.; Tagawa, Y.; Lee, C.-H.; Aoyama, T.; Ichihara, G.; Furuhashi, K.; Kamijima, M.; Gonzalez, F.J.; et al. Di(2-ethylhexyl)phthalate induces hepatic tumorigenesis through a peroxisome proliferator-activated receptor alpha-independent pathway. J. Occup. Health 2007, 49, 172–182. [Google Scholar] [CrossRef]
- Wang, Y.-C.; Chen, H.-S.; Long, C.-Y.; Tsai, C.-F.; Hsieh, T.-H.; Hsu, C.-Y.; Tsai, E.-M. Possible mechanism of phthalates-induced tumorigenesis. Kaohsiung J. Med. Sci. 2012, 28, S22–S27. [Google Scholar] [CrossRef] [PubMed]
- Butterworth, B.E.; Bermudez, E.; Smith-Oliver, T.; Earle, L.; Cattley, R.; Martin, J.; Popp, J.A.; Strom, S.; Jirtle, R.; Michalopoulos, G. Lack of genotoxic activity of di(2-ethylhexyl)phthalate (DEHP) in rat and human hepatocytes | Carcinogenesis | Oxford Academic. Carcinogenesis 1984, 5, 1329–1335. [Google Scholar] [CrossRef]
- Benjamin, S.; Masai, E.; Kamimura, N.; Takahashi, K.; Anderson, R.C.; Faisal, P.A. Phthalates impact human health: Epidemiological evidences and plausible mechanism of action. J. Hazard. Mater. 2017, 340, 360–383. [Google Scholar] [CrossRef] [PubMed]
- Miao, Y.; Wang, R.; Lu, C.; Zhao, J.; Deng, Q. Lifetime cancer risk assessment for inhalation exposure to di(2-ethylhexyl) phthalate (DEHP). Environ. Sci. Pollut. Res. Int. 2017, 24, 312–320. [Google Scholar] [CrossRef]
- United States Environmental Protection Agency. Integrated Risk Information System: Di(2-ethylhexyl) Phthalate (DEHP) (CASRN 117-81-7). Available online: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0014_summary.pdf (accessed on 22 August 2020).
- Berardis, S.; Sokal, E. Pediatric non-alcoholic fatty liver disease: An increasing public health issue. Eur. J. Pediatr. 2014, 173, 131–139. [Google Scholar] [CrossRef] [PubMed]
- Fausto, N.; Campbell, J.S. The role of hepatocytes and oval cells in liver regeneration and repopulation. Mech. Dev. 2003, 120, 117–130. [Google Scholar] [CrossRef]
- Huch, M.; Dorrell, C.; Boj, S.F.; van Es, J.H.; Li, V.S.W.; van de Wetering, M.; Sato, T.; Hamer, K.; Sasaki, N.; Finegold, M.J.; et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 2013, 494, 247–250. [Google Scholar] [CrossRef]
- Kholodenko, I.V.; Yarygin, K.N. Cellular mechanisms of liver regeneration and cell-based therapies of liver diseases. Biomed Res. Int. 2017, 2017, 8910821. [Google Scholar] [CrossRef]
- Sadri, A.-R.; Jeschke, M.G.; Amini-Nik, S. Advances in liver regeneration: Revisiting hepatic stem/progenitor cells and their origin. Stem Cells Int. 2016, 2016, 7920897. [Google Scholar] [CrossRef]
- Canovas-Jorda, D.; Louisse, J.; Pistollato, F.; Zagoura, D.; Bremer, S. Regenerative toxicology: The role of stem cells in the development of chronic toxicities. Expert Opin. Drug Metab. Toxicol. 2014, 10, 39–50. [Google Scholar] [CrossRef]
- Kang, K.-S.; Trosko, J.E. Stem cells in toxicology: Fundamental biology and practical considerations. Toxicol. Sci. 2011, 120, S269–S289. [Google Scholar] [CrossRef] [PubMed]
- Knight, B.; Lim, R.; Yeoh, G.C.; Olynyk, J.K. Interferon-gamma exacerbates liver damage, the hepatic progenitor cell response and fibrosis in a mouse model of chronic liver injury. J. Hepatol. 2007, 47, 826–833. [Google Scholar] [CrossRef]
- Persano, L.; Zagoura, D.; Louisse, J.; Pistollato, F. Role of environmental chemicals, processed food derivatives, and nutrients in the induction of carcinogenesis. Stem Cells Dev. 2015, 24, 2337–2352. [Google Scholar] [CrossRef]
- Vanova, T.; Raska, J.; Babica, P.; Sovadinova, I.; Kunova Bosakova, M.; Dvorak, P.; Blaha, L.; Rotrekl, V. Freshwater Cyanotoxin Cylindrospermopsin Has Detrimental Stage-specific Effects on hepatic differentiation from human embryonic stem cells. Toxicol. Sci. 2019, 168, 241–251. [Google Scholar] [CrossRef] [PubMed]
- Wang, K.; Sun, D. Cancer stem cells of hepatocellular carcinoma. Oncotarget 2018, 9, 23306–23314. [Google Scholar] [CrossRef] [PubMed]
- Vondráček, J.; Machala, M.; Vondracek, J.; Machala, M.; Vondráček, J.; Machala, M. Environmental ligands of the aryl hydrocarbon receptor and their effects in models of adult liver progenitor cells. Stem Cells Int. 2016, 2016, 4326194. [Google Scholar] [CrossRef]
- Hernández-Guerra, M.; Hadjihambi, A.; Jalan, R. Gap junctions in liver disease: Implications for pathogenesis and therapy. J. Hepatol. 2019, 70, 759–772. [Google Scholar] [CrossRef]
- Maes, M.; Vinken, M. Connexin-based signaling and drug-induced hepatotoxicity. J. Clin. Transl. Res. 2017, 3, 189–198. [Google Scholar] [CrossRef]
- Aasen, T.; Mesnil, M.; Naus, C.C.; Lampe, P.D.; Laird, D.W. Gap junctions and cancer: Communicating for 50 years. Nat. Rev. Cancer 2016, 16, 775–788. [Google Scholar] [CrossRef]
- Sai, K.; Upham, B.L.; Kang, K.S.; Hasegawa, R.; Inoue, T.; Trosko, J.E. Inhibitory effect of pentachlorophenol on gap junctional intercellular communication in rat liver epithelial cells in vitro. Cancer Lett. 1998, 130, 9–17. [Google Scholar] [CrossRef]
- Trosko, J.E.; Ruch, R.J. Cell-cell communication in carcinogenesis. Front. Biosci. 1998, 3, d208–d236. [Google Scholar] [CrossRef] [PubMed]
- Trosko, J.E.; Ruch, R.J. Gap junctions as targets for cancer chemoprevention and chemotherapy. Curr. Drug Targets 2002, 3, 465–482. [Google Scholar] [CrossRef] [PubMed]
- Vinken, M. Gap junctions and non-neoplastic liver disease. J. Hepatol. 2012, 57, 655–662. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Vinken, M.; Doktorova, T.; Decrock, E.; Leybaert, L.; Vanhaecke, T.; Rogiers, V. Gap junctional intercellular communication as a target for liver toxicity and carcinogenicity. Crit. Rev. Biochem. Mol. Biol. 2009, 44, 201–222. [Google Scholar] [CrossRef] [PubMed]
- Yamasaki, H.; Omori, Y.; Zaidan-Dagli, M.L.; Mironov, N.; Mesnil, M.; Krutovskikh, V. Genetic and epigenetic changes of intercellular communication genes during multistage carcinogenesis. Cancer Detect. Prev. 1999, 23, 273–279. [Google Scholar] [CrossRef]
- Jacobs, M.N.; Colacci, A.; Corvi, R.; Vaccari, M.; Aguila, M.C.; Corvaro, M.; Delrue, N.; Desaulniers, D.; Ertych, N.; Jacobs, A.; et al. Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens. Arch. Toxicol. 2020, 1, 3. [Google Scholar] [CrossRef]
- Hu, W.; Jones, P.D.; Upham, B.L.; Trosko, J.E.; Lau, C.; Giesy, J.P. Inhibition of gap junctional intercellular communication by perfluorinated compounds in rat liver and dolphin kidney epithelial cell lines in vitro and Sprague-Dawley rats in vivo. Toxicol. Sci. 2002, 68, 429–436. [Google Scholar] [CrossRef]
- Kubincova, P.; Sychrova, E.; Raska, J.; Basu, A.; Yawer, A.; Dydowiczova, A.; Babica, P.; Sovadinova, I. Polycyclic aromatic hydrocarbons and endocrine disruption: Role of testicular gap junctional intercellular communication and connexins. Toxicol. Sci. 2019, 169, 70–83. [Google Scholar] [CrossRef]
- Osgood, R.S.; Upham, B.L.; Hill, T., 3rd; Helms, K.L.; Velmurugan, K.; Babica, P.; Bauer, A.K. Polycyclic aromatic hydrocarbon-induced signaling events relevant to inflammation and tumorigenesis in lung cells are dependent on molecular structure. PLoS ONE 2014, 8, e65150. [Google Scholar] [CrossRef]
- Sovadinova, I.; Babica, P.; Boke, H.; Kumar, E.; Wilke, A.; Park, J.-S.; Trosko, J.E.; Upham, B.L. Phosphatidylcholine specific PLC-induced dysregulation of gap junctions, a robust cellular response to environmental toxicants, and prevention by resveratrol in a rat liver cell model. PLoS ONE 2015, 10, e0124454. [Google Scholar] [CrossRef]
- Upham, B.L.; Sovadinova, I.; Babica, P.; Sovadinová, I.; Babica, P. Gap junctional intercellular communication: A functional biomarker to assess adverse effects of toxicants and toxins, and health benefits of natural products. J. Vis. Exp. 2016, 2016. [Google Scholar] [CrossRef] [PubMed]
- Upham, B.L.; Park, J.-S.; Babica, P.; Sovadinova, I.; Rummel, A.M.; Trosko, J.E.; Hirose, A.; Hasegawa, R.; Kanno, J.; Sai, K. Structure-activity-dependent regulation of cell communication by perfluorinated fatty acids using in vivo and in vitro model systems. Environ. Health Perspect. 2009, 117, 545–551. [Google Scholar] [CrossRef] [PubMed]
- Upham, B.L.; Blaha, L.; Babica, P.; Park, J.-S.; Sovadinova, I.; Pudrith, C.; Rummel, A.M.; Weis, L.M.; Sai, K.; Tithof, P.K.; et al. Tumor promoting properties of a cigarette smoke prevalent polycyclic aromatic hydrocarbon as indicated by the inhibition of gap junctional intercellular communication via phosphatidylcholine-specific phospholipase C. Cancer Sci. 2008, 99, 696–705. [Google Scholar] [CrossRef] [PubMed]
- Babica, P.; Zurabian, R.; Kumar, E.R.; Chopra, R.; Mianecki, M.J.; Park, J.-S.; Jasa, L.; Trosko, J.E.; Upham, B.L. Methoxychlor and vinclozolin induce rapid changes in intercellular and intracellular signaling in liver progenitor cells. Toxicol. Sci. 2016, 153, 174–185. [Google Scholar] [CrossRef]
- Klaunig, J.E.; Ruch, R.J.; DeAngelo, A.B.; Kaylor, W.H. Inhibition of mouse hepatocyte intercellular communication by phthalate monoesters. Cancer Lett. 1988, 43, 65–71. [Google Scholar] [CrossRef]
- Tsao, M.S.; Smith, J.D.; Nelson, K.G.; Grisham, J.W. A diploid epithelial cell line from normal adult rat liver with phenotypic properties of “oval” cells. Exp. Cell Res. 1984, 154, 38–52. [Google Scholar] [CrossRef]
- Dydowiczová, A.; Brózman, O.; Babica, P.; Sovadinová, I.; Dydowiczova, A.; Brozman, O.; Babica, P.; Sovadinova, I. Improved multiparametric scrape loading-dye transfer assay for a simultaneous high-throughput analysis of gap junctional intercellular communication, cell density and viability. Sci. Rep. 2020, 10, 730. [Google Scholar] [CrossRef]
- Lawan, A.; Bennett, A.M. Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism. Trends Endocrinol. Metab. 2017, 28, 868–878. [Google Scholar] [CrossRef]
- McMullen, P.D.; Bhattacharya, S.; Woods, C.G.; Pendse, S.N.; McBride, M.T.; Soldatow, V.Y.; Deisenroth, C.; LeCluyse, E.L.; Clewell, R.A.; Andersen, M.E. Identifying qualitative differences in PPARα signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods. Toxicol. Vitr. 2020, 64, 104463. [Google Scholar] [CrossRef]
- Mathieu-Denoncourt, J.; Wallace, S.J.; de Solla, S.R.; Langlois, V.S. Plasticizer endocrine disruption: Highlighting developmental and reproductive effects in mammals and non-mammalian aquatic species. Gen. Comp. Endocrinol. 2015, 219, 74–88. [Google Scholar] [CrossRef]
- Ambe, K.; Sakakibara, Y.; Sakabe, A.; Makino, H.; Ochibe, T.; Tohkin, M. Comparison of the developmental/reproductive toxicity and hepatotoxicity of phthalate esters in rats using an open toxicity data source. J. Toxicol. Sci. 2019, 44, 245–255. [Google Scholar] [CrossRef] [PubMed]
- Han, H.; Lee, H.A.; Park, B.; Park, B.; Hong, Y.S.; Ha, E.H.; Park, H. Associations of phthalate exposure with lipid levels and insulin sensitivity index in children: A prospective cohort study. Sci. Total Environ. 2019, 662, 714–721. [Google Scholar] [CrossRef] [PubMed]
- Milosevic, N.; Milic, N.; Zivanovic Bosic, D.; Bajkin, I.; Percic, I.; Abenavoli, L.; Medic Stojanoska, M. Potential influence of the phthalates on normal liver function and cardiometabolic risk in males. Environ. Monit. Assess. 2017, 190, 17. [Google Scholar] [CrossRef]
- Trasande, L.; Spanier, A.J.; Sathyanarayana, S.; Attina, T.M.; Blustein, J. Urinary phthalates and increased insulin resistance in adolescents. Pediatrics 2013, 132, e646–e655. [Google Scholar] [CrossRef] [PubMed]
- Praveena, S.M.; Teh, S.W.; Rajendran, R.K.; Kannan, N.; Lin, C.-C.; Abdullah, R.; Kumar, S. Recent updates on phthalate exposure and human health: A special focus on liver toxicity and stem cell regeneration. Environ. Sci. Pollut. Res. Int. 2018, 25, 11333–11342. [Google Scholar] [CrossRef]
- Rusyn, I.; Peters, J.M.; Cunningham, M.L. Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver. Crit. Rev. Toxicol. 2006, 36, 459–479. [Google Scholar] [CrossRef]
- Maes, M.; Yanguas, S.C.; Willebrords, J.; Vinken, M. Models and methods for in vitro testing of hepatic gap junctional communication. Toxicol. Vitr. 2015, 30, 569–577. [Google Scholar] [CrossRef]
- Smith, J.H.; Isenberg, J.S.; Pugh, G.J.; Kamendulis, L.M.; Ackley, D.; Lington, A.W.; Klaunig, J.E. Comparative in vivo hepatic effects of Di-isononyl phthalate (DINP) and related C7-C11 dialkyl phthalates on gap junctional intercellular communication (GJIC), peroxisomal beta-oxidation (PBOX), and DNA synthesis in rat and mouse liver. Toxicol. Sci. 2000, 54, 312–321. [Google Scholar] [CrossRef]
- Pugh, G.J.; Isenberg, J.S.; Kamendulis, L.M.; Ackley, D.C.; Clare, L.J.; Brown, R.; Lington, A.W.; Smith, J.H.; Klaunig, J.E. Effects of di-isononyl phthalate, di-2-ethylhexyl phthalate, and clofibrate in cynomolgus monkeys. Toxicol. Sci. 2000, 56, 181–188. [Google Scholar] [CrossRef]
- Isenberg, J.S.; Kamendulis, L.M.; Smith, J.H.; Ackley, D.C.; Pugh, G.J.; Lington, A.W.; Klaunig, J.E. Effects of Di-2-ethylhexyl phthalate (DEHP) on gap-junctional intercellular communication (GJIC), DNA synthesis, and peroxisomal beta oxidation (PBOX) in rat, mouse, and hamster liver. Toxicol. Sci. 2000, 56, 73–85. [Google Scholar] [CrossRef]
- McKee, R.H. The role of inhibition of gap junctional intercellular communication in rodent liver tumor induction by phthalates: Review of data on selected phthalates and the potential relevance to man. Regul. Toxicol. Pharm. 2000, 32, 51–55. [Google Scholar] [CrossRef] [PubMed]
- Melnick, R.L. Is peroxisome proliferation an obligatory precursor step in the carcinogenicity of di(2-ethylhexyl)phthalate (DEHP)? Environ. Health Perspect. 2001, 109, 437–442. [Google Scholar] [CrossRef] [PubMed]
- Kamendulis, L.M.; Isenberg, J.S.; Smith, J.H.; Pugh, G.J.; Lington, A.W.; Klaunig, J.E. Comparative effects of phthalate monoesters on gap junctional intercellular communication and peroxisome proliferation in rodent and primate hepatocytes. J. Toxicol. Environ. Health. A 2002, 65, 569–588. [Google Scholar] [CrossRef] [PubMed]
- Pham, N.; Iyer, S.; Hackett, E.; Lock, B.H.; Sandy, M.; Zeise, L.; Solomon, G.; Marty, M. Using ToxCast to explore chemical activities and hazard traits: A case study with ortho-phthalates. Toxicol. Sci. 2016, 151, 286–301. [Google Scholar] [CrossRef] [PubMed]
- Corton, J.C.; Peters, J.M.; Klaunig, J.E. The PPARα-dependent rodent liver tumor response is not relevant to humans: Addressing misconceptions. Arch. Toxicol. 2018, 92, 83–119. [Google Scholar] [CrossRef]
- Guyton, K.Z.; Chiu, W.A.; Bateson, T.F.; Jinot, J.; Scott, C.S.; Brown, R.C.; Caldwell, J.C. A reexamination of the PPAR-alpha activation mode of action as a basis for assessing human cancer risks of environmental contaminants. Environ. Health Perspect. 2009, 117, 1664–1672. [Google Scholar] [CrossRef]
- Rusyn, I.; Corton, J.C. Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate. Mutat. Res. 2012, 750, 141–158. [Google Scholar] [CrossRef]
- Li, L.; Zhao, G.-D.; Shi, Z.; Qi, L.-L.; Zhou, L.-Y.; Fu, Z.-X. The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC. Oncol. Lett. 2016, 12, 3045–3050. [Google Scholar] [CrossRef]
- Tsai, C.-F.; Hsieh, T.-H.; Lee, J.-N.; Hsu, C.-Y.; Wang, Y.-C.; Lai, F.-J.; Kuo, K.-K.; Wu, H.-L.; Tsai, E.-M.; Kuo, P.-L. Benzyl butyl phthalate induces migration, invasion, and angiogenesis of Huh7 hepatocellular carcinoma cells through nongenomic AhR/G-protein signaling. BMC Cancer 2014, 14, 556. [Google Scholar] [CrossRef]
- Hayashi, T.; Nomata, K.; Chang, C.C.; Ruch, R.J.; Trosko, J.E. Cooperative effects of v-myc and c-Ha-ras oncogenes on gap junctional intercellular communication and tumorigenicity in rat liver epithelial cells. Cancer Lett. 1998, 128, 145–154. [Google Scholar] [CrossRef]
- Rae, R.S.; Mehta, P.P.; Chang, C.C.; Trosko, J.E.; Ruch, R.J. Neoplastic phenotype of gap-junctional intercellular communication-deficient WB rat liver epithelial cells and its reversal by forced expression of connexin 32. Mol. Carcinog. 1998, 22, 120–127. [Google Scholar] [CrossRef]
- Sun, H.; Liu, G. Chemopreventive effect of dimethyl dicarboxylate biphenyl on malignant transformation of WB-F344 rat liver epithelial cells. Acta Pharm. Sin. 2005, 26, 1339–1344. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Li, Y.; Kang, X.; Guo, K.; Li, H.; Gao, D.; Sun, L.; Liu, Y. Dynamic alteration of protein expression profiles during neoplastic transformation of rat hepatic oval-like cells. Cancer Sci. 2010, 101, 1099–1107. [Google Scholar] [CrossRef] [PubMed]
- Solan, J.L.; Lampe, P.D. Connexin43 phosphorylation: Structural changes and biological effects. Biochem. J. 2009, 419, 261–272. [Google Scholar] [CrossRef]
- Ruch, R.J.; Trosko, J.E.; Madhukar, B.V. Inhibition of connexin43 gap junctional intercellular communication by TPA requires ERK activation. J. Cell. Biochem. 2001, 83, 163–169. [Google Scholar] [CrossRef]
- Rivedal, E.; Opsahl, H. Role of PKC and MAP kinase in EGF- and TPA-induced connexin43 phosphorylation and inhibition of gap junction intercellular communication in rat liver epithelial cells. Carcinogenesis 2001, 22, 1543–1550. [Google Scholar] [CrossRef]
- Wang, Y.; Zhu, H.; Kannan, K. A review of biomonitoring of phthalate exposures. Toxics 2019, 7, 21. [Google Scholar] [CrossRef]
- Hogberg, J.; Hanberg, A.; Berglund, M.; Skerfving, S.; Remberger, M.; Calafat, A.M.; Filipsson, A.F.; Jansson, B.; Johansson, N.; Appelgren, M.; et al. Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ. Health Perspect. 2008, 116, 334–339. [Google Scholar] [CrossRef]
- Wan, H.T.; Leung, P.Y.; Zhao, Y.G.; Wei, X.; Wong, M.H.; Wong, C.K.C. Blood plasma concentrations of endocrine disrupting chemicals in Hong Kong populations. J. Hazard. Mater. 2013, 261, 763–769. [Google Scholar] [CrossRef]
- Chen, J.; Liu, H.; Qiu, Z.; Shu, W. Analysis of di-n-butyl phthalate and other organic pollutants in Chongqing women undergoing parturition. Environ. Pollut. 2008, 156, 849–853. [Google Scholar] [CrossRef]
- Kim, S.H.; Chun, S.; Jang, J.Y.; Chae, H.D.; Kim, C.-H.; Kang, B.M. Increased plasma levels of phthalate esters in women with advanced-stage endometriosis: A prospective case-control study. Fertil. Steril. 2011, 95, 357–359. [Google Scholar] [CrossRef] [PubMed]
- Reddy, B.S.; Rozati, R.; Reddy, B.V.R.; Raman, N.V.V.S.S. Association of phthalate esters with endometriosis in Indian women. BJOG 2006, 113, 515–520. [Google Scholar] [CrossRef] [PubMed]
- Reddy, B.S.; Rozati, R.; Reddy, S.; Kodampur, S.; Reddy, P.; Reddy, R. High plasma concentrations of polychlorinated biphenyls and phthalate esters in women with endometriosis: A prospective case control study. Fertil. Steril. 2006, 85, 775–779. [Google Scholar] [CrossRef] [PubMed]
- El-Fouly, M.H.; Trosko, J.E.; Chang, C.-C. Scrape-loading and dye transfer: A rapid and simple technique to study gap junctional intercellular communication. Exp. Cell Res. 1987, 168, 422–430. [Google Scholar] [CrossRef]
- Babica, P.; Sovadinová, I.; Upham, B.L. Scrape Loading/Dye Transfer Assay. In Gap Junction Protocols; Vinken, M., Johnstone, S.R., Eds.; Springer: New York, NY, USA, 2016; Volume 1437, pp. 133–144. ISBN 978-1-4939-3664-9. [Google Scholar]
- Schneider, C.A.; Rasband, W.S.; Eliceiri, K.W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 2012, 9, 671. [Google Scholar] [CrossRef]
- Raska, J.; Ctverackova, L.; Dydowiczova, A.; Sovadinova, I.; Blaha, L.; Babica, P. Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells. Toxicol. Appl. Pharm. 2018, 345, 103–113. [Google Scholar] [CrossRef]
- Rozen, S.; Skaletsky, H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol. Biol. 2000, 132, 365–386. [Google Scholar] [CrossRef]
- Dukic, A.R.; McClymont, D.W.; Tasken, K. A Cell-based high-throughput assay for gap junction communication suitable for assessing connexin 43-Ezrin interaction disruptors using IncuCyte ZOOM. Slas Discov. Adv. Life Sci. R D 2017, 22, 77–85. [Google Scholar] [CrossRef][Green Version]
- Picoli, C.; Soleilhac, E.; Journet, A.; Barette, C.; Comte, M.; Giaume, C.; Mouthon, F.; Fauvarque, M.-O.; Charveriat, M. High-content screening identifies new inhibitors of connexin 43 gap junctions. Assay Drug Dev. Technol. 2019, 17, 240–248. [Google Scholar] [CrossRef]
Phthalate | Carbon Chain Length | MW a g/mol | Log Kow a | Group | GJIC | MAPK-Erk1/2 Activation | |
---|---|---|---|---|---|---|---|
0.5hEC50b (µM) | 80μMET50c (min) | FOC d (0.5 h) | |||||
MMP Monomethyl phthalate | Short | 180 | 9 × 10−1 to 1.50 | A | >200 | >1440 | 0 |
DMP Dimethyl phthalate | Short | 194 | 1.46 to 1.90 | A | >200 | >1440 | 0 |
DEP Diethyl phthalate | Short | 222 | 2.21 to 3 | A | >200 | >1440 | 0 |
MBP Monobutyl phthalate | Medium | 222 | 2.37 to 3.07 | A | >200 | >1440 | 0 |
DPrP Dipropyl phthalate | Short | 250 | 3.14 to 3.87 | B | 70 | >1440 | 5 |
DIPrP Diisopropyl phthalate | Short | 250 | 2.61 to 3.48 | B | 86 | >1440 | 8 |
DAP Diallyl phthalate | Short | 246 | 2.92 to 3.36 | B | 100 | >1440 | 5 |
DBP Dibutyl phthalate | Medium | 278 | 4.39 to 4.83 | C | 13 | 2 | 24 |
DIBP Diisibutyl phthalate | Medium | 278 | 3.81 to 4.46 | C | 17 | 10 | 32 |
BBP Benzyl butyl phthalate | Medium | 312 | 3.57 to 4.91 | C | 21 | 2 | 21 |
DPeP Dipentyl phthalate | Medium | 306 | 5.19 to 5.89 | C | 16 | 10 | 32 |
DCHP Dicyclohexyl phthalate | Medium | 330 | 4.79 to 6.20 | C | 22 | 10 | 28 |
DPhP Diphenyl phthalate | Medium | 318 | 2.82 to 4.61 | C | 39 | 10 | 7 |
DHpP Diheptyl phthalate | Long | 363 | 5.65–6.82 | D | 58 | 25 | 4 |
DIHpP Diisoheptyl phthalate | Long | 363 | 7.4 | D | 44 | 17 | 4 |
DEHP Di-(2-ethylhexyl) phthalate | Long | 391 | 5.11–8.35 | E | >200 | 207 | 3 |
DOP Dioctyl phthalate | Long | 391 | 7.84 to 9.08 | E | >200 | 292 | 3 |
DINP Diisononyl phthalate | Long | 419 | 8.57 to 11.2 | E | >200 | 711 | 5 |
DDP Didecyl phthalate | Long | 447 | 9.05 | F | >200 | >1440 | 4 |
DIDP Diisodecyl phthalate | Long | 447 | 10.36 | F | >200 | >1440 | 4 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Čtveráčková, L.; Jančula, D.; Raška, J.; Babica, P.; Sovadinová, I. Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells. Int. J. Mol. Sci. 2020, 21, 6069. https://doi.org/10.3390/ijms21176069
Čtveráčková L, Jančula D, Raška J, Babica P, Sovadinová I. Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells. International Journal of Molecular Sciences. 2020; 21(17):6069. https://doi.org/10.3390/ijms21176069
Chicago/Turabian StyleČtveráčková, Lucie, Daniel Jančula, Jan Raška, Pavel Babica, and Iva Sovadinová. 2020. "Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells" International Journal of Molecular Sciences 21, no. 17: 6069. https://doi.org/10.3390/ijms21176069
APA StyleČtveráčková, L., Jančula, D., Raška, J., Babica, P., & Sovadinová, I. (2020). Structure-Dependent Effects of Phthalates on Intercellular and Intracellular Communication in Liver Oval Cells. International Journal of Molecular Sciences, 21(17), 6069. https://doi.org/10.3390/ijms21176069