Metabolic activation of 2,6-xylidine in the nasal olfactory mucosa and the mucosa of the upper alimentary and respiratory tracts in rats

Toxicological Sciences

Volumn 81, Issue 2, 2004, Pages 263-272

  Tydén, Eva ^a   Tjälve, Hans ^a   Larsson, Pia ^a  

^a SWEDISH UNIVERSITY OF AGRICULTURAL SCIENCES   (Sweden)

Author keywords

2,6 xylidine; Alimentary tract; Metabolic activation; Nasal cancer; Nasal olfactory mucosa; Respiratory tract

Indexed keywords

N,N DIMETHYLANILINE; TRITIUM;

ABDOMEN; ADIPOSE TISSUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY DISTRIBUTION; CARCINOGENICITY; CONTROLLED STUDY; CORRELATION ANALYSIS; FEMALE; FREEZE DRYING; IN VITRO STUDY; ISOTOPE LABELING; LUMINESCENCE; METABOLIC ACTIVATION; NONHUMAN; OLFACTORY EPITHELIUM; RAT; SOLUBILITY; SOLVENT EXTRACTION; SUBCUTANEOUS TISSUE; TISSUE SECTION; TOXICOKINETICS; UPPER GASTROINTESTINAL TRACT; UPPER RESPIRATORY TRACT; WHOLE BODY AUTORADIOGRAPHY; WHOLE BODY RADIATION;

ANILINE COMPOUNDS; ANIMALS; AUTORADIOGRAPHY; BIOTRANSFORMATION; DNA; FEMALE; FREEZE DRYING; MOUTH MUCOSA; NASAL MUCOSA; PROTEIN BINDING; PROTEINS; RATS; RATS, SPRAGUE-DAWLEY; RESPIRATORY MUCOSA; SUBCELLULAR FRACTIONS; TISSUE DISTRIBUTION; WHOLE-BODY COUNTING;

EID: 5744238402     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/kfh219     Document Type: Article

References (44)

1. Bahrami, F., Brittebo, E. B., Bergman, A., Larsson, C., and Brandt, I. (1999). Localization and comparative toxicity of methylsulfonyl-2,5- and 2,6-dichlorobenzene in the olfactory mucosa of mice. Toxicol. Sci. 49, 116-123.
2. Baker, M. T., and Van Dyke, R. A. (1984). Metabolism-dependent binding of the chlorinated insecticide DDT and its metabolite, DDD, to microsomal protein and lipids. Biochem. Pharmacol. 33, 255-260.
3. Brandt, I., Brittebo, E. B., Feil, V. J., and Bakke, J. E. (1990). Irreversible binding and toxicity of the herbicide dichlobenil (2,6-dichlorobenzonitrile) in the olfactory mucosa of mice. Toxicol. Appl. Pharmacol. 103, 491-501.
4. Brittebo, E. B. (1997). Metabolism-dependent activation and toxicity of chemicals in nasal glands. Mutat/Res. 380, 61-75.
5. Brittebo, E. B., Eriksson, C., Feil, V., Bakke, J., and Brandt, I. (1991). Toxicity of 2,6-dichlorothiobenzamide (chlorthiamid) and 2,6-dichlorobenzamide in the olfactory nasal mucosa of mice. Fundam. Appl. Toxicol. 17, 92-102.
6. Bryant, M. S., Simmons, H. F., Harrell, R. E., and Hinson, J. A. (1994). 2,6-Dimethylaniline-hemoglobin adducts from lidocaine in humans. Carcinogenesis 15, 2287-2290.
7. Ding, X., and Kaminsky, L. S. (2003). Human extrahepatic cytochromes P450: Function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu. Rev. Pharmacol. Toxicol. 43, 149-73.
8. Ding, X., Spink, D. C., Bhama, J. K., Sheng, J. J., Vaz, A. D., and Coon, M. J. (1996). Metabolic activation of 2,6-dichlorobenzonitrile, an olfactory-specific toxicant, by rat, rabbit, and human cytochromes P450. Mol. Pharmacol. 49, 1113-1121.
9. Dureja, P., Tanwar, R. S., and Choudhary, P. P. (2000). Identification of impurities in technical metalaxyl. Chemosphere 41, 1407-1410.
10. Franzén, A., Carlsson, C., Brandt, I., and Brittebo, E. B. (2003). Isomer-specific bioactivation and toxicity of dichlorophenyl methylsulphone in rat olfactory mucosa. Toxicol. Pathol. 31, 364-372.
11. Gan, J., Skipper, P. L., and Tannenbaum, S. R. (2001). Oxidation of 2,6-dimethylaniline by recombinant human cytochrome P450s and human liver microsomes. Chem. Res. Toxicol. 14, 672-677.
12. Ghantous, H., Lofberg, B., Tjälve, H., Danielsson, B. R., and Dencker, L. (1988). Extrahepatic sites of metabolism of halothane in the rat. Pharmacol. Toxicol. 62, 135-141.
13. Gopalakrishnan, R., Morse, M. A., Lu, J., Weghorst, C. M., Sabourin, C. L., Stoner, G. D., and Murphy, S. E. (1999). Expression of cytochrome P450 2A3 in rat esophagus: Relevance to N-nitrosobenzylmethylamine. Carcinogenesis 20, 885-891.
14. IARC (International Agency for Research on Cancer). (1993) IARC Monographs on the Evaluation of the Carcinogenic Risks of Chemicals to Humans Vol.57, 2,6-dimethylaniline (2,6-xylidine , pp. 323-335, IARC Press, Lyons, France.
15. Irvine, W. J., and Saxby, M. J. (1969). Steam volatile amines of Lataki tobacco leaf. Phytochemistry 8, 473-476.
16. Jeffrey, A. M., Luo, F. Q., Amin, S., Krzeminski, J., Zech, K., and Williams, G. M. (2002). Lack of DNA binding in the rat nasal mucosa and other tissues of the nasal toxicants roflumilast, a phosphodiesterase 4 inhibitor, and a metabolite, 4-amino-3,5-dichloropyridine, in contrast to the nasal carcinogen 2,6-dimethylaniline. Drug Chem. Toxicol. 25, 93-107.
17. Keenaghan, J. B., and Boyes, R. N. (1972). The tissue distribution, metabolism and excretion of lidocaine in rats, guinea pigs, dogs and man. J. Pharmacol. Exp. Ther. 180, 454-463.
18. Kornreich, M., and Montgomery, C. A., Jr. (1990). Toxicology and Carcinogenesis Studies of 2,6-xylidine (2,6-dimethylaniline) in Charles River CD Rats. National Toxicology Program (NTP). NTP TR 278, NIH Publication No. 90-2534, pp. 1-138.
19. 1 in extra-hepatic tissues of various animal species. Thesis from the Swedish University of Agricultural Sciences, Uppsala, Sweden (ISBN 91-576-4805-0).
20. Larsson, P., and Tjälve, H. (1988). Tracing tissues with 4-ipomeanol-metabolizing capacity in rats. Chem. Biol. Interact. 67, 1-24.
21. Löfberg, B., and Tjälve, H. (1986). Tracing tissues with chloroform-metabolizing capacity in rats. Toxicology 39, 13-35.
22. Marques, M. M., Mourato, L. L., Amorim, M. T., Santos, M. A., Melchior, W. B., Jr., and Beland, F. A. (1997). Effect of substitution site upon the oxidation potentials of alkylanilines, the mutagenicities of N-hydroxyalkylanilines, and the conformations of alkylaniline-DNA adducts. Chem. Res. Toxicol. 10, 1266-1274.
23. Marques, M., Gamboa da Costa, G., Blankenship, L. R., Culp, S. J., and Beland, F. A. (2002). The effect of deuterium and fluorine substitution upon the mutagenicity of N-hydroxy-2,6-dimethylaniline. Mutat. Res. 506-507, 41-48.
24. Martin, S. W., Bishop, F. E., Kerr, B. M., Moor, M., Moore, M., Sheffels, P., Rashed, M., Slatter, J. G., Berthon-Cedille, L., Lepage, F., Descombe, J. J., Picard, M., Baillie, T. A., and Levy, R. H. (1997). Pharmacokinetics and metabolism of the novel anticonvulsant agent N-(2,6-dimethylphenyl)-5-methyl-3-isoxazolecarboxamide (D2624) in rats and humans. Drug Metab. Dispos. 25, 40-46.
25. Parker, R. J., Collins, J. M., and Strong, J. M. (1996). Identification of 2,6-xylidine as a major lidocaine metabolite in human liver slices. Drug Metab. Dispos. 24, 1167-1173.
26. Patrinakos, C., and Hoffman, D. (1979). Chemical studies of tobacco smoke. LXIV. On analysis of aromatic amines in cigarette smoke. J. Anal. Toxicol. 3, 150-154.
27. Pinto, L. F., Moraes, E., Albano, R. M., Silva, M. C., Godoy, W., Glisovic, T., and Lang, M. A. (2001). Rat oesophageal cytochrome P450 (CYP) monooxygenase system: comparison to the liver and relevance in N-nitrosodiethylamine carcinogenesis. Carcinogenesis 22, 1877-1883.
28. Puente, N. W., and Josephy, P. D. (2001). Analysis of the lidocaine metabolite 2,6-dimethylaniline in bovine and human milk. J. Anal. Toxicol. 25, 711-715.
29. Pütter, J., and Sagner, G. (1973). Chemical studies to detect residues of xylazine hydrochloride. Vet. Med. Rev. 2, 145-159.
30. Ringe, D., Turesky, R. J., Skipper, P. L., and Tannenbaum, S. R. (1988). Structure of the single stable hemoglobin adduct formed by 4-aminobiphenyl in vivo. Chem. Res. Toxicol. 1, 22-24.
31. Shimizu, M., Lasker, J. M., Tsutsumi, M., and Lieber, C. S. (1990). Immunohistochemical localization of ethanol-inducible P450IIE1 in the rat alimentary tract. Gastroenterology 99, 1044-1053.
32. Short, C. R., Hardy, M. L., and Barker, S. A. (1989a). The in vivo oxidative metabolism of 2,4- and 2,6-dimethylaniline in the dog and rat. Toxicology 57, 45-58.
33. Short, C. R., Joseph, M., and Hardy, M. L. (1989b). Covalent binding of [14C]-2,6-dimethylaniline to DNA of rat liver and ethmoid turbinate. J. Toxicol. Environ. Health 27, 85-94.
34. Singer, V. L., Jones, L. J., Yue, S. T., and Haugland, R. P. (1997). Characterization of PicoGreen reagent and development of a fluorescence-based solution assay for double-stranded DNA quantitation. Anal. Biochem. 249, 228-238.
35. Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., and Klenk, D. C. (1985). Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76-85.
36. Thomas, J., Morgan, D., and Vine, J. (1976). Metabolism of etidocaine in man. Xenobiotica 6, 39-48.
37. Thornton-Manning, J. R., and Dahl, A. R. (1997). Metabolic capacity of nasal tissue interspecies comparisons of xenobiotic-metabolizing enzymes. Mutat. Res. 380, 43-59.
38. Tjälve, H., and Löfberg, B. (1983). Extrahepatic sites of metabolism of carbon tetrachloride in rats. Chem. Biol. Interact. 46, 299-316.
39. Tjälve, H. (1991). The tissue distribution and the tissue specificity of bioactivation of some tobacco-specific and some other N-nitrosamines. Crit Rev. Toxicol. 21, 265-294.
40. Tjälve, H., Larsson, P., Andersson, C., and Busk, L. (1992). Bioactivation of aflatoxin B1 in the bovine olfactory mucosa: DNA binding, mutagenicity and induction of sister chromatid exchanges. Carcinogenesis 13, 1345-1350.
41. Ullberg, S., Larsson, B., and Tjälve, H. (1982). Autoradiography. In Biologic Application of Radiotracers (H.J. Glenn, ed.), pp. 56-108. CRC Press, Inc., Boca Raton, FL.
42. Watt, K. C., Plopper, C. G., Weir, A. J., Tarkington, B., and Buckpitt, A. R. (1998). Cytochrome P450 2E1 in rat tracheobronchial airways: Response to ozone exposure. Toxicol. Appl. Pharmacol. 149, 195-202.
43. Yasuhara, K., Kobayashi, H., Shimamura, Y., Koujitani, T., Onodera, H., Takagi, H., Hirose, M., and Mitsumori, K. (2000). Toxicity and blood concentrations of xylazine and its metabolite, 2,6-dimethylaniline, in rats after single or continuous oral administrations. J. Toxicol. Sci. 25, 105-113.
44. Zalipsky, J. J., Won, C. M., and Patel, D. M. (1978). Analytical-physical profile of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent. Arzneimittelforschung 28, 1441-1447.