Acute and Chronic Exposure of Toluene Induces Genotoxicity in Different Regions of the Brain in Normal and Allergic Mouse Models
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Toluene is a widely used industrial organic solvent and is ubiquitous in our environment. The neurobehavioral and neurotoxic effects of toluene are well recognized; however, its genotoxicity is still under discussion. Toluene biotransformation leads to the generation of reactive oxygen species that cause oxidative stress and DNA damages. Individuals with different immunogenetic backgrounds have different sensitivities to toxic chemical exposure. Previous studies have suggested that allergic stimulation may influence the threshold for toluene sensitivity due to the modulation of neurotrophin-related genes. Therefore, we aimed to investigate toluene-induced genotoxicity in different brain regions following acute and chronic exposure in vivo and to further examine whether allergic stimulation may influence the sensitivity to toluene-induced genotoxicity. In this present study, we found that exposure of toluene induced oxidative DNA damages resulting in genotoxicity in different brain regions including cortex, cerebellum, and hippocampus using comet assay. Higher genotoxicity induced by toluene was observed in the hippocampus of control mice compared to OVA-immunized mice. These results provide evidence that toluene-induced genotoxicity may contribute to its neurotoxicity in different immunogenetic individuals.
KeywordsToluene Genotoxicity Acute and chronic exposure Hippocampus BDNF
T.-Y.L., C.-C.C., H.-H.T., T.-Y.L., and H.-T.W. designed research; T.-Y.L., C.-C.C., H.-H.T., T.-Y.L., and H.-T.W. performed research; T.-Y.L. and H.-T.W. analyzed data; and T.-Y.L. and H.-T.W. wrote the paper.
This work was supported by the Ministry of Science and Technology, Taiwan, under [106-3114-B-010001 (H-T Wang); 107-2320-B-010-018 (H-T Wang)].
Compliance with Ethical Standards
The use of animals has been approved by the Institutional Animal Care and Use Committee of Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. All experiments were performed in accordance with the approved guidelines.
Conflict of Interest
The authors declare that they have no conflicts of interest.
- ACGIH (American Conference of Governmental Industrial Hygienists). (2007) TLVs and BEIs: Based on the documentation of the threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati, OH.Google Scholar
- (ATSDR) AfTSaDR (2000) Toxicological profile for toluene. Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA, p 30341Google Scholar
- Callan SP, Hannigan JH, Bowen SE (2017b) Prenatal toluene exposure impairs performance in the Morris water maze in adolescent rats. Neuroscience 342:180–187. https://doi.org/10.1016/j.neuroscience.2015.08.050 CrossRefPubMedGoogle Scholar
- EPA U (2005) Toxicological review of tolueneGoogle Scholar
- Gelazonia L, Japaridze N, Svanidze I (2006) Pyramidal cell loss in hippocampus of young rats exposed to toluene. Georgian Med News:126–128Google Scholar
- IARC (1999) Monographs on the evaluation of carcinogenic risk to humans, re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide Agency for Research on Cancer, Toluene, vol 71. World Health Organization, LyonGoogle Scholar
- Ladefoged O, Hougaard KS, Hass U, Sorensen IK, Lund SP, Svendsen GW, Lam HR (2004) Effects of combined prenatal stress and toluene exposure on apoptotic neurodegeneration in cerebellum and hippocampus of rats. Basic Clin Pharmacol Toxicol 94:169–176. https://doi.org/10.1111/j.1742-7843.2004.pto940403.x CrossRefPubMedGoogle Scholar
- Martinez-Alfaro M, Palma-Tirado L, Sandoval-Zapata F, Carabez-Trejo A (2006) Correlation between formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites determined by a comet assay, increased MDA, and decreased glutathione during long exposure to thinner inhalation. Toxicol Lett 163:198–205. https://doi.org/10.1016/j.toxlet.2005.10.021 CrossRefPubMedGoogle Scholar
- Moro AM, Brucker N, Charão M, Bulcão R, Freitas F, Baierle M, Nascimento S, Valentini J, Cassini C, Salvador M, Linden R, Thiesen F, Buffon A, Moresco R, Garcia SC (2012) Evaluation of genotoxicity and oxidative damage in painters exposed to low levels of toluene. Mutat Res 746:42–48. https://doi.org/10.1016/j.mrgentox.2012.02.007 CrossRefPubMedGoogle Scholar
- von Euler M, Pham TM, Hillefors M, Bjelke B, Henriksson B, von Euler G (2000) Inhalation of low concentrations of toluene induces persistent effects on a learning retention task, beam-walk performance, and cerebrocortical size in the rat. Exp Neurol 163:1–8. https://doi.org/10.1006/exnr.1999.7288 CrossRefGoogle Scholar
- Wetmore BA, Struve MF, Gao P, Sharma S, Allison N, Roberts KC, Letinski DJ, Nicolich MJ, Bird MG, Dorman DC (2008) Genotoxicity of intermittent co-exposure to benzene and toluene in male CD-1 mice. Chem Biol Interact 173:166–178. https://doi.org/10.1016/j.cbi.2008.03.012 CrossRefPubMedGoogle Scholar
- Win-Shwe TT, Kunugita N, Yamamoto S, Arashidani K, Fujimaki H (2010a) Strain differences influence N-methyl-D-aspartate receptor subunit gene expression in the olfactory bulb of an allergic mouse model following toluene exposure. Neuroimmunomodulation 17:340–347. https://doi.org/10.1159/000292028 CrossRefPubMedGoogle Scholar
- Win-Shwe TT, Tsukahara S, Yamamoto S, Fukushima A, Kunugita N, Arashidani K, Fujimaki H (2010b) Up-regulation of neurotrophin-related gene expression in mouse hippocampus following low-level toluene exposure. Neurotoxicology 31:85–93. https://doi.org/10.1016/j.neuro.2009.11.004 CrossRefPubMedGoogle Scholar