Effects of Chlorpyrifos and Trichloropyridinol on HEK 293 Human Embryonic Kidney Cells

Overview

Journal Chemosphere

Specialties Biology
Chemistry
Environmental Health

Date 2017 Oct 24

PMID 29059561

Citations 6

Authors

Jeanette M Van Emon

Peipei Pan

Frank van Breukelen

Affiliations

Soon will be listed here.

Abstract

Chlorpyrifos (CPF) [O, O-diethyl -O-3, 5, 6-trichloro-2-pyridyl phosphorothioate] is an organophosphate insecticide widely used for agricultural and urban pest control. Trichloropyridinol (TCP; 3,5,6-trichloro-2-pyridinol), the primary metabolite of CPF, is often used as a generic biomarker of exposure for CPF and related compounds. Human embryonic kidney 293 (HEK 293) cells were exposed to CPF and TCP with varying concentrations and exposure periods. Cell cultures enable the cost-effective study of specific biomarkers to help determine toxicity pathways to predict the effects of chemical exposures without relying on whole animals. Both CPF and TCP were found to induce cytotoxic effects with CPF being more toxic than TCP with EC values of 68.82 μg/mL and 146.87 μg·ml respectively. Cell flow cytometric analyses revealed that exposure to either CPF or TCP leads to an initial burst of apoptotic induction followed by a slow recruitment of cells leading towards further apoptosis. CPF produced a strong induction of IL6, while TCP exposure resulted in a strong induction of IL1α. Importantly, the concentrations of CPF and TCP required for these cytokine inductions were higher than those required to induce apoptosis. These data suggest CPF and TCP are cytotoxic to HEK 293 cells but that the mechanism may not be related to an inflammatory response. CPF and TCP also varied in their effects on the HEK 293 proteome with 5 unique proteins detected after exposure to CPF and 31 unique proteins after TCP exposure.

Citing Articles

3,5,6-Tri-chloro-pyridin-2-ol.

Vaughn T, Soheil S, Ogundele O, Fronczek F, Uppu R IUCrdata. 2024; 9(Pt 11):x241126.

PMID: 39649088 PMC: 11618871. DOI: 10.1107/S241431462401126X.

Tris (2-chloroisopropyl) phosphate and Tris (nonylphenyl) phosphite Promote Human Renal Cell Apoptosis through the ERK/CEPBA/Long Non-Coding RNA Cytoskeleton Regulator Axis.

Zhao H, Yan Y, Gao Y, Wang J, Li S Toxics. 2024; 12(7).

PMID: 39058104 PMC: 11281261. DOI: 10.3390/toxics12070452.

Decontamination of Chlorpyrifos Residue in Soil by Using (Lamiales: Lamiaceae) for Phytoremediation and Two Bacterial Strains.

Aioub A, Fahmy M, Ammar E, Maher M, Ismail H, Yue J Toxics. 2024; 12(6).

PMID: 38922115 PMC: 11209611. DOI: 10.3390/toxics12060435.

Unveiling the Aftermath: Exploring Residue Profiles of Insecticides, Herbicides, and Fungicides in Rice Straw, Soils, and Air Post-Mixed Pesticide-Contaminated Biomass Burning.

Lamnoi S, Boonupara T, Sumitsawan S, Vongruang P, Prapamontol T, Udomkun P Toxics. 2024; 12(1).

PMID: 38251041 PMC: 10819870. DOI: 10.3390/toxics12010086.

Histopathological features of low-dose organophosphate exposure.

Cobilinschi C, Tincu R, Cobilinschi C, Neagu T, Becheanu G, Sinescu R Rom J Morphol Embryol. 2021; 61(2):423-432.

PMID: 33544793 PMC: 7864311. DOI: 10.47162/RJME.61.2.11.

References

Das P, Cao Y, Rose R, Cherrington N, Hodgson E . Enzyme induction and cytotoxicity in human hepatocytes by chlorpyrifos and N,N-diethyl-m-toluamide (DEET). Drug Metabol Drug Interact. 2009; 23(3-4):237-60. DOI: 10.1515/dmdi.2008.23.3-4.237. View

Eaton D, Daroff R, Autrup H, Bridges J, Buffler P, Costa L . Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment. Crit Rev Toxicol. 2008; 38 Suppl 2:1-125. DOI: 10.1080/10408440802272158. View

Rouquie D, Heneweer M, Botham J, Ketelslegers H, Markell L, Pfister T . Contribution of new technologies to characterization and prediction of adverse effects. Crit Rev Toxicol. 2015; 45(2):172-83. DOI: 10.3109/10408444.2014.986054. View

Nakadai A, Li Q, Kawada T . Chlorpyrifos induces apoptosis in human monocyte cell line U937. Toxicology. 2006; 224(3):202-9. DOI: 10.1016/j.tox.2006.04.055. View

Liu L, Xu Y, Xu L, Wang J, Wu W, Xu L . Analysis of differentially expressed proteins in zebrafish (Danio rerio) embryos exposed to chlorpyrifos. Comp Biochem Physiol C Toxicol Pharmacol. 2014; 167:183-9. DOI: 10.1016/j.cbpc.2014.10.006. View

Adeleye Y, Andersen M, Clewell R, Davies M, Dent M, Edwards S . Implementing Toxicity Testing in the 21st Century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment. Toxicology. 2014; 332:102-11. DOI: 10.1016/j.tox.2014.02.007. View

Focke W, van der Westhuizen I, Musee N, Loots M . Kinetic interpretation of log-logistic dose-time response curves. Sci Rep. 2017; 7(1):2234. PMC: 5440384. DOI: 10.1038/s41598-017-02474-w. View

Chambers J, CHAMBERS H . Oxidative desulfuration of chlorpyrifos, chlorpyrifos-methyl, and leptophos by rat brain and liver. J Biochem Toxicol. 1989; 4(3):201-3. DOI: 10.1002/jbt.2570040310. View

Koch H, Hardt J, Angerer J . Biological monitoring of exposure of the general population to the organophosphorus pesticides chlorpyrifos and chlorpyrifos-methyl by determination of their specific metabolite 3,5,6-trichloro-2-pyridinol. Int J Hyg Environ Health. 2002; 204(2-3):175-80. DOI: 10.1078/1438-4639-00082. View

10.

AMER S, Aly F . Cytogenetic effects of pesticides. IV. Cytogenetic effects of the insecticides Gardona and Dursban. Mutat Res. 1992; 279(3):165-70. DOI: 10.1016/0165-1218(92)90063-6. View

11.

Ishiyama M, Miyazono Y, Sasamoto K, Ohkura Y, Ueno K . A highly water-soluble disulfonated tetrazolium salt as a chromogenic indicator for NADH as well as cell viability. Talanta. 1997; 44(7):1299-305. DOI: 10.1016/s0039-9140(97)00017-9. View

12.

Willett C, Rae J, Goyak K, Landesmann B, Minsavage G, Westmoreland C . Pathway-based toxicity: history, current approaches and liver fibrosis and steatosis as prototypes. ALTEX. 2014; 31(4):407-21. DOI: 10.14573/altex.1401283. View

13.

Timchalk C, Poet T, Kousba A . Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos. Toxicology. 2005; 220(1):13-25. DOI: 10.1016/j.tox.2005.11.011. View

14.

Grafstrom R, Nymark P, Hongisto V, Spjuth O, Ceder R, Willighagen E . Toward the Replacement of Animal Experiments through the Bioinformatics-driven Analysis of 'Omics' Data from Human Cell Cultures. Altern Lab Anim. 2015; 43(5):325-32. DOI: 10.1177/026119291504300506. View

15.

Slotkin T, Seidler F . Oxidative and excitatory mechanisms of developmental neurotoxicity: transcriptional profiles for chlorpyrifos, diazinon, dieldrin, and divalent nickel in PC12 cells. Environ Health Perspect. 2009; 117(4):587-96. PMC: 2679603. DOI: 10.1289/ehp.0800251. View

16.

Albers J, Garabrant D, Schweitzer S, Garrison R, Richardson R, Berent S . The effects of occupational exposure to chlorpyrifos on the peripheral nervous system: a prospective cohort study. Occup Environ Med. 2004; 61(3):201-11. PMC: 1740727. DOI: 10.1136/oem.2003.008847. View

17.

Racke K . Environmental fate of chlorpyrifos. Rev Environ Contam Toxicol. 1993; 131:1-150. DOI: 10.1007/978-1-4612-4362-5_1. View

18.

Moura H, Terilli R, Woolfitt A, Gallegos-Candela M, McWilliams L, Solano M . Studies on botulinum neurotoxins type /C1 and mosaic/DC using Endopep-MS and proteomics. FEMS Immunol Med Microbiol. 2011; 61(3):288-300. DOI: 10.1111/j.1574-695X.2010.00774.x. View

19.

Estevan C, Vilanova E, Sogorb M . Chlorpyrifos and its metabolites alter gene expression at non-cytotoxic concentrations in D3 mouse embryonic stem cells under in vitro differentiation: considerations for embryotoxic risk assessment. Toxicol Lett. 2012; 217(1):14-22. DOI: 10.1016/j.toxlet.2012.11.026. View

20.

Spiegel M, Weber F . Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus. Virol J. 2006; 3:17. PMC: 1444920. DOI: 10.1186/1743-422X-3-17. View