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Toxicologic Pathology
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Development of Methodology for the Three-Dimensional Modelling of the Metabolic Capacity of the Rat Nasal Cavity using Glutathione S-Transferase M1 as an Example

Darren A. Robinson

School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, United Kingdom

John R. Foster

AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom

John A. Nash

Syngenta CTL, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, United Kingdom

Celia J. Reed

School of Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, United Kingdom, c.j.reed{at}livjm.ac.uk

A variety of chemicals induce site-specific lesions in the rodent nasal cavity. In order to explore the reasons for this site-selectivity, methodology for (a) creation of a 3-dimensional (3D) model of a rat nasal cavity, and (b) mapping of semiquantitative data onto the model has been developed. The head of a rat was fixed, decalcified, step-sectioned (every 100 µm) and stained with hematoxylin and eosin. Digital images of the sections were optically captured, and a KS400 image analysis system (Imaging Associates, Thame, Oxford, UK), attached to a standard personal computer, was used to align adjacent images and reconstruct the series in 3D. The final model was anatomically correct, and could be rotated in any plane and manipulated to display individual internal structures. The spatial localization of a glutathione S-transferase (rGSTM1, previously known as GST 3-3) within this model was investigated using immunohistochemistry. Step sections (every 400 µm) were stained, analyzed by imaging densitometry, and the results for the stained regions within the nasal cavity divided into 4 grades representing high to low expression of rGSTM1. The data was mapped onto the 3D model and showed that the highest expression of this enzyme was in the central regions of the nasal cavity at the transition between respiratory and olfactory epithelia. This methodology will allow investigation of the relationship between the in situ localization of bioactivating and detoxifying enzyme systems and the site-specificity of nasal lesions.

Key Words: 3D modelling • glutathione S-transferase • rGSTM1 • rat • nasal cavity.

References

  • Banger KK, Foster JR, Lock EA, Reed CJ ( 1994). Immunohistochemical localisation of six glutathione S-transferases within the nasal cavity of the rat. Arch Toxicol 69: 91—98.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Banger KK, Lock EA, Reed CJ ( 1993). The characterization of glutathione S-transferases from rat olfactory epithelium. Biochem J 290: 199—204.[Web of Science][Medline] [Order article via Infotrieve]
  • Bogdanffy MS, Gladnick NL, Kegelman T., Frame SR (1997). Four-week inhalation cell proliferation study of the effects of vinyl acetate on rat nasal epithelium. Inhalation Toxicol 9: 331—350.[CrossRef][Web of Science]
  • Bogdanffy MS, Randall HW, Morgan KT (1986). Histochemical localisation of aldehyde dehydrogenase in the respiratory tract of the Fischer-344 rat. Toxicol Appl Pharmacol 82: 560—567.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bogdanffy MS, Randall HW, Morgan KT (1987). Biochemical quantitation and histochemical localisation of carboxylesterase in the nasal passages of the Fischer-344 rat and B6C3F1 mouse. Toxicol Appl Pharmacol 88: 183—194.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Brandt I., Brittebo EB, Feil VJ, Bakke JE (1990). Irreversible binding and toxicity of the herbicide dichlobenil (2,6-dichlorobenzonitrile) in the olfactory mucosa of mice. Toxicol Appl Pharmacol 103: 491—501.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bush ML, Frederick CB, Kimbell JS, Ultman JS (1998). A CFD-PBPK hybrid model for simulating gas and vapor uptake in the rat nose. Toxicol Appl Pharmacol 150: 133—145.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Dahl AR, Hadley WM (1991). Nasal cavity enzymes involved in xenobiotic metabolism: Effects on the toxicity of inhalants. CRC Crit Rev Toxicol 21: 345—372.[CrossRef]
  • Evans JE, Miller ML, Andringa A., Hastings L. (1995). Behavioral, histological, and neurochemical effects of nickel (II) on the rat olfactory system. Toxicol Appl Pharmacol 130: 209—220.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gaskell BA, Hext PM, Pigott GH, Hodge MCH, Tinston DJ (1988). Olfactory and hepatic changes following inhalation of 3-trifluoromethyl pyridine in rats. Toxicology 50: 57—68.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Harkema JR (1991). Comparative aspects of nasal airway anatomy: Relevance to inhalation toxicology. Toxicol Pathol 19: 321—336.[Web of Science][Medline] [Order article via Infotrieve]
  • Hart SGE, Cartun RW, Wyand DS, Khairallah EA, Cohen SD (1995). Immunohistochemical localization of acetaminophen in target tissues of the cd-1 mouse-correspondence of covalent binding with toxicity. Fundamen Appl Toxicol 24: 260—274.[CrossRef]
  • Hext PM, Pinto PJ, Gaskell BA (2001). Methyl methacrylate toxicity in rat nasal epithelium: Investigation of the time course of lesion development and recovery from short term vapour inhalation. Toxicology 156: 119—128.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Johansson SL (1981). Carcinogenicity of analgesics: Long-term treatment of Sprague—Dawley rats with phenacetin, phenazone, caffeine and paracetamol (acetaminophen). Int J Cancer 27: 521—529.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Keenan CM, Kelly DP, Bogdanffy MS (1990). Degeneration and recovery of rat olfactory epithelium following inhalation of dibasic esters. Fundamen Appl Toxicol 15: 381—393.[CrossRef]
  • Kepler GM, Joyner DR, Fleishman A., Richardson RB, Gross EA, Morgan KT, Godo MN, Kimbell JS (1995). Method for obtaining accurate geometrical co-ordinates of nasal airways for computer dosimetry modelling and lesion mapping. Inhalation Toxicol 7: 1207—1224.[CrossRef][Web of Science]
  • Kepler GM, Richardson RB, Morgan KT, Kimbell JS (1998). Computer simulation of inspiratory nasal airflow and inhaled gas uptake in a rhesus monkey. Toxicol Appl Pharmacol 150: 1—11.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kimbell JS, Fleishman A., Andersen ME, Morgan KT (1990). Determination of nasal airflow characteristics in F344 rats and rhesus monkeys and application to inhalation toxicology. Toxicologist 10: 259.
  • Kimbell JS, Godo MN, Gross EA, Joyner DR, Richardson RB, Morgan KT (1997). Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages. Toxicol Appl Pharmacol 145: 388—398.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kimbell JS, Gross EA, Joyner DR, Godo MN, Morgan KT (1993). Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat. Toxicol Appl Pharmacol 121: 253—263.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kimbell JS, Gross EA, Richardson RB, Conolly RB, Morgan KT (1997). Correlation of regional formaldehyde flux predictions with the distribution of formaldehyde-induced squamous metaplasia in F344 rat nasal passages. Mut Res 380: 143—154.[Web of Science][Medline] [Order article via Infotrieve]
  • Mery S., Gross EA, Joyner DR, Godo MN, Morgan KT (1993). Nasal diagrams—A tool for recording the distribution of nasal lesions in rats and mice. Toxicol Pathol 22: 353—372.[Web of Science]
  • Morgan KT (1997). A brief review of formaldehyde carcinogenesis in relation to rat nasal pathology and human health risk assessment. Toxicol Pathol 25: 291—307.[Abstract/Free Full Text]
  • Morgan KT, Gross EA, Joyner DR, Ishmael J., Thake D. (1997). Proliferative nasal lesions induced in rats by alachlor, acetochlor and butachlor originate in specific regions of the olfactory mucosa. Toxicologist 36: 112.
  • Morgan KT, Kimbell JS, Monticello TM, Patra AL, Leishman A. (1991). Studies of inspiratory airflow patterns in the nasal passages of the F344 rat and rhesus monkey using nasal molds: Relevance to formaldehyde toxicity. Toxicol Appl Pharmacol 110: 223—240.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Morgan KT, Monticello TM, Fleishman A., Patra AL (1989). Preparation of rat nasal airway casts and their application to studies of nasal airflow. In: Extrapolation of Dosimetric Relationships for Inhaled Particles and Gases, Crapo JD, Miller FJ, Hayes AW (eds). Academic Press Inc, San Diego, pp 45—58.
  • Reed CJ (1993). Drug metabolism in the nasal cavity: Relevance to toxicology. Drug Met Rev 25: 173—205.[Web of Science][Medline] [Order article via Infotrieve]
  • Reed CJ, Gaskell BA, Banger KK, Lock EA ( 1995). Olfactory toxicity of methyl iodide in the rat. Arch Toxicol 70: 51—56.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Subramaniam RP, Richardson RB, Morgan KT, Kimbell JS, Guilmette RA (1998). Computational fluid dynamics simulations of inspiratory airflow in the human nose and nasopharynx. Inhalation Toxicol 10: 91—120.[CrossRef][Web of Science]
  • Thornton-Manning JR, Dahl AR (1997). Metabolic capacity of nasal tissue interspecies comparisons of xenobiotic-metabolizing enzymes. Mut Res 380: 43—59.[Web of Science][Medline] [Order article via Infotrieve]
  • Turk MAM, Henk WG, Flory W. (1987). 3-Methylindole-induced nasal mucosal damage in mice. Vet Pathol 24: 400—403.[Abstract]
  • Uraih LC, Maronpot RR (1990). Normal histology of the nasal cavity and application of special techniques. Environ Health Perspect 85: 187—208.[Web of Science][Medline] [Order article via Infotrieve]
  • Voigt JM, Guengerich FP, Baron J. (1993). Localization and induction of cytochrome-P450 1A1 and aryl hydrocarbon hydroxylase activity in rat nasal mucosa. J Histochem Cytochem 41: 877—885.[Abstract]
  • Zissu D. (1995). Histopathological changes in the respiratory tract of mice exposed to ten families of airborne chemicals. J Appl Toxicol 15: 207—213.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 31, No. 3, 332-339 (2003)
DOI: 10.1080/01926230390204397
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