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Immediate responses of the cockroach Blaptica dubia after the exposure to sulfur mustard

  • Molecular Toxicology
  • Published:
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Abstract

The chemical agent sulfur mustard (SM) causes erythema, skin blisters, ulcerations, and delayed wound healing. It is accepted that the underlying molecular toxicology is based on DNA alkylation. With an expected delay, DNA damage causes impairment of protein biosynthesis and disturbance of cell division. However, using the cockroach model Blaptica dubia, the presented results show that alkylating compounds provoke immediate behavior responses along with fast changes in the electrical field potential (EFP) of neurons, suggesting that lesions of DNA are probably not the only effect of alkylating compounds. Blaptica dubia was challenged with SM or 2-chloroethyl-ethyl sulfide (CEES). Acute toxicity was objectified by a disability score. Physiological behavior responses (antennae pullback reflex, escape attempts, and grooming) were monitored after exposure. To estimate the impact of alkylating agents on neuronal activity, EFP recordings of the antennae and the thoracic ganglion were performed. After contact to neat SM, a pullback reflex of the antennae was the first observation. Subsequently, a striking escape behavior occured which was characterized by persistent movement of the legs. In addition, an instantaneous processing of the electrical firing pattern from the antennae to the descending ganglia was detectable. Remarkably, comparing the toxicity of the applied alkylating agents, effects induced by CEES were much more pronounced compared to SM. In summary, our findings document immediate effects of B. dubia after exposure to alkylating substances. These fast responses cannot be interpreted as a consequence of DNA alkylation. Therefore, the dogma that DNA alkylation is the exclusive cause for SM toxicity has to be questioned.

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Abbreviations

AITC:

Allylisothiocyanate

CEES:

2-Chloroethyl-ethyl sulfide

DS:

Disability score

EtOH:

Ethanol

PST:

Peristimulus time

TRPA1:

Transient receptor potential cation channel A1

SM:

Sulfur mustard, bis-(2-chloroethyl) sulfide

References

  • Baba Y, Tsukada A, Comer CM (2010) Collision avoidance by running insects: antennal guidance in cockroaches. J Exp Biol 213(Pt 13):2294–2302. doi:10.1242/jeb.036996

    Article  PubMed  Google Scholar 

  • Batal M, Boudry I, Mouret S, Wartelle J, Emorine S, Bertoni M, Bérard I, Cléry-Barraud C, Douki T (2013) Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin. Toxicol Appl Pharmacol 273(3):644–650. doi:10.1016/j.taap.2013.10.010

    Article  CAS  PubMed  Google Scholar 

  • Bennett SR (1984) Environmental hazards of chemical agent simulants. CRDC-TR-84055, Aberdeen Proving Ground, MD

  • Bennett RA, Behrens E, Zinn A, Duncheon C, Lamkin TJ (2014) Mustard gas surrogate, 2-chloroethyl ethylsulfide (2-CEES), induces centrosome amplification and aneuploidy in human and mouse cells: 2-CEES induces centrosome amplification and chromosome instability. Cell Biol Toxicol 30(4):195–205. doi:10.1007/s10565-014-9279-0

    Article  CAS  PubMed  Google Scholar 

  • Boroczky K, Wada-Katsumata A, Batchelor D, Zhukovskaya M, Schal C (2013) Insects groom their antennae to enhance olfactory acuity. Proc Natl Acad Sci USA 110(9):3615–3620. doi:10.1073/pnas.1212466110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camhi JM (1988) Escape behavior in the cockroach: distributed neural processing. Experientia 44(5):401–408. doi:10.1007/BF01940534

    Article  CAS  PubMed  Google Scholar 

  • Cataldo DA (1988) Acute environmental toxicity and persistence of a chemical agent simulant: 2-chloroethyl ethyl sulfid (CEES), Aberdeen Proving Ground, MD

  • Domenici P, Booth D, Blagburn JM, Bacon JP (2009) Escaping away from and towards a threat: the cockroach’s strategy for staying alive. Commun Integr Biol 2(6):497–500

    Article  PubMed  PubMed Central  Google Scholar 

  • Fouad K, Rathmayer W, Libersat F (1996) Neuromodulation of the escape behavior of the cockroach Periplaneta americana by the venom of the parasitic wasp Ampulex compressa. J Comp Physiol A 178(1):91. doi:10.1007/BF00189593

    Article  Google Scholar 

  • French AS, Meisner S, Liu H, Weckström M, Torkkeli PH (2015) Transcriptome analysis and RNA interference of cockroach phototransduction indicate three opsins and suggest a major role for TRPL channels. Front Physiol 6:207. doi:10.3389/fphys.2015.00207

    Article  PubMed  PubMed Central  Google Scholar 

  • Frings H, Frings M (1949) The loci of contact chemoreceptors in insects. A review with new evidence. Am Midl Nat 41(3):602. doi:10.2307/2421776

    Article  Google Scholar 

  • Georghiou GP (1972) The evolution of resistance to pesticides. Annu Rev Ecol Syst 3(1):133–168. doi:10.1146/annurev.es.03.110172.001025

    Article  CAS  Google Scholar 

  • Hinterwirth A, Zeiner R, Tichy H (2004) Olfactory receptor cells on the cockroach antennae: responses to the direction and rate of change in food odour concentration. Eur J Neurosci 19(12):3389–3392. doi:10.1111/j.0953-816X.2004.03386.x

    Article  PubMed  Google Scholar 

  • Kehe K, Szinicz L (2005) Medical aspects of sulphur mustard poisoning. Toxicology 214(3):198–209. doi:10.1016/j.tox.2005.06.014

    Article  CAS  PubMed  Google Scholar 

  • Kehe K, Balszuweit F, Steinritz D, Thiermann H (2009) Molecular toxicology of sulfur mustard-induced cutaneous inflammation and blistering. Toxicology 263(1):12–19. doi:10.1016/j.tox.2009.01.019

    Article  CAS  PubMed  Google Scholar 

  • Lockey JK, Willis MA (2015) One antenna, two antennae, big antennae, small: total antennae length, not bilateral symmetry, predicts odor-tracking performance in the American cockroach Periplaneta americana. J Exp Biol 218(Pt 14):2156–2165. doi:10.1242/jeb.117721

    Article  PubMed  Google Scholar 

  • Loudon C, Bustamante J, Kellogg DW (2014) Cricket antennae shorten when bending (Acheta domesticus L.). Front Physiol 5:242. doi:10.3389/fphys.2014.00242

    Article  PubMed  PubMed Central  Google Scholar 

  • Maliszewska J, Tegowska E (2016) Capsazepine affects thermal preferences of the American cockroach (Blattodea: Blattidae). Eur J Entomol 113:315–319. doi:10.14411/eje.2016.040

    Article  Google Scholar 

  • Mangerich A, Debiak M, Birtel M, Ponath V, Balszuweit F, Lex K, Martello R, Burckhardt-Boer W, Strobelt R, Siegert M, Thiermann H, Steinritz D, Schmidt A, Bürkle A (2016) Sulfur and nitrogen mustards induce characteristic poly(ADP-ribosyl)ation responses in HaCaT keratinocytes with distinctive cellular consequences. Toxicol Lett 244:56–71. doi:10.1016/j.toxlet.2015.09.010

    Article  CAS  PubMed  Google Scholar 

  • Masta A, Gray PJ, Phillips DR (1996) Effect of sulphur mustard on the initiation and elongation of transcription. Carcinogenesis 17(3):525–532

    Article  CAS  PubMed  Google Scholar 

  • Mongeau J-M, Sponberg SN, Miller JP, Full RJ (2015) Sensory processing within cockroach antenna enables rapid implementation of feedback control for high-speed running maneuvers. J Exp Biol 218(Pt 15):2344–2354. doi:10.1242/jeb.118604

    Article  PubMed  Google Scholar 

  • Munro NB, Talmage SS, Griffin GD, Waters LC, Watson AP, King JF, Hauschild V (1999) The sources, fate, and toxicity of chemical warfare agent degradation products. Environ Health Perspect 107(12):933–974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nansen C, Baissac O, Nansen M, Powis K, Baker G (2016) Behavioral avoidance-will physiological insecticide resistance level of insect strains affect their oviposition and movement responses? PLoS One 11(3):e0149994. doi:10.1371/journal.pone.0149994

    Article  PubMed  PubMed Central  Google Scholar 

  • Olszewska J, Tęgowska E (2011) Opposite effect of capsaicin and capsazepine on behavioral thermoregulation in insects. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 197(10):1021–1026. doi:10.1007/s00359-011-0657-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pearson GS (1993) Veterans at risk the health effects of mustard gas and Lewisite. National Acad Press, Washington

    Google Scholar 

  • Pita R (2009) Toxin weapons: from World War I to jihadi terrorism. Toxin Rev 28(4):219–237. doi:10.3109/15569540903246136

    Article  CAS  Google Scholar 

  • Pita R, Anadon A (2015) Chemical weapons of mass destruction and terrorism: chapter 7. Elsevier Science, Burlington

    Book  Google Scholar 

  • Robinson WH (1996) Antennal grooming and movement behaviour in the German cockroach, Blattella germanica (L.). In: Proceedings of the 2nd International conference on insect pests in urban environment, pp 361–370

  • Sfara V, Mougabure-Cueto GA, Gonzalez-Audino PA (2016) Modulation of the behavioral and electrical responses to the repellent DEET elicited by the pre-exposure to the same compound in Blattella germanica. PeerJ 4:e2150. doi:10.7717/peerj.2150

    Article  PubMed  PubMed Central  Google Scholar 

  • Shakarjian MP, Heck DE, Gray JP, Sinko PJ, Gordon MK, Casillas RP, Heindel ND, Gerecke DR, Laskin DL, Laskin JD (2010) Mechanisms mediating the vesicant actions of sulfur mustard after cutaneous exposure. Toxicol Sci Off J Soc Toxicol 114(1):5–19. doi:10.1093/toxsci/kfp253

    Article  CAS  Google Scholar 

  • Stenger B, Zehfuss F, Mückter H, Schmidt A, Balszuweit F, Schäfer E, Büch T, Gudermann T, Thiermann H, Steinritz D (2015) Activation of the chemosensing transient receptor potential channel A1 (TRPA1) by alkylating agents. Arch Toxicol 89(9):1631–1643. doi:10.1007/s00204-014-1414-4

    Article  CAS  PubMed  Google Scholar 

  • Stenger B, Popp T, John H, Siegert M, Tsoutsoulopoulos A, Schmidt A, Muckter H, Gudermann T, Thiermann H, Steinritz D (2017) N-Acetyl-l-cysteine inhibits sulfur mustard-induced and TRPA1-dependent calcium influx. Arch Toxicol 91(5):2179–2189. doi:10.1007/s00204-016-1873-x

    Article  CAS  PubMed  Google Scholar 

  • Wada-Katsumata A, Silverman J, Schal C (2011) Differential inputs from chemosensory appendages mediate feeding responses to glucose in wild-type and glucose-averse German cockroaches, Blattella germanica. Chem Sens 36(7):589–600. doi:10.1093/chemse/bjr023

    Article  CAS  Google Scholar 

  • Wicher D, Agricola H-J, Schönherr R, Heinemann SH, Derst C (2006) TRPgamma channels are inhibited by cAMP and contribute to pacemaking in neurosecretory insect neurons. J Biol Chem 281(6):3227–3236. doi:10.1074/jbc.M511741200

    Article  CAS  PubMed  Google Scholar 

  • Worek F, Seeger T, Neumaier K, Wille T, Thiermann H (2016) Blaptica dubia as sentinels for exposure to chemical warfare agents—a pilot study. Toxicol Lett 262:12–16. doi:10.1016/j.toxlet.2016.09.006

    Article  CAS  PubMed  Google Scholar 

  • Zhukovskaya M, Yanagawa A, Forschler BT (2013) Grooming behavior as a mechanism of insect disease defense. Insects 4(4):609–630. doi:10.3390/insects4040609

    Article  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Tanja Popp and Robin Lüling have contributed equally.

Authors and Affiliations

  1. Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstraße 11, 80937, Munich, Germany

    Tanja Popp, Robin Lüling, Thomas Seeger, Horst Thiermann, Franz Worek & Dirk Steinritz

  2. Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilian-University Munich, Goethestraße 33, 80336, Munich, Germany

    Tanja Popp, Ingrid Boekhoff, Thomas Gudermann & Dirk Steinritz

  3. Division of Neurobiology, Department Biology II, Ludwig-Maximilian-University, Munich, Germany

    Francisco Branoner

Authors
  1. Tanja Popp
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  2. Robin Lüling
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  3. Ingrid Boekhoff
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  4. Thomas Seeger
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  5. Francisco Branoner
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Correspondence to Tanja Popp.

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Electronic supplementary material

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Detailed information about significances of the statistical analyses for figures 2–5. (PDF 581 kb)

204_2017_2064_MOESM2_ESM.mp4

Cockroach was placed in a tube with a droplet of SM. Cockroach moves towards the agent, tips into the droplet, and shows the pullback reflex. Behavior is shown in slow motion. (MP4 2321 kb)

204_2017_2064_MOESM3_ESM.mp4

After sensing the alkylating agent in the beaker glass, cockroaches try to escape including fast, parallel, and coordinated leg kicks of all three leg pairs (shown in slow motion from 15th seconds onwards) which turned finally into uncontrolled, spasmodical leg movements (shown in slow motion (from 24th seconds onwards). (MP4 5571 kb)

204_2017_2064_MOESM4_ESM.mp4

When cockroaches get in touch with any substance, they start cleaning their antennae and mouthparts. The video shows a slow motion of grooming behavior. (MP4 1716 kb)

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Popp, T., Lüling, R., Boekhoff, I. et al. Immediate responses of the cockroach Blaptica dubia after the exposure to sulfur mustard. Arch Toxicol 92, 337–346 (2018). https://doi.org/10.1007/s00204-017-2064-0

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