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ToxSci Advance Access originally published online on July 14, 2004
Toxicological Sciences 2004 81(2):263-272; doi:10.1093/toxsci/kfh219
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Toxicological Sciences vol. 81 no. 2 © Society of Toxicology 2004; all rights reserved.

Metabolic Activation of 2,6-Xylidine in the Nasal Olfactory Mucosa and the Mucosa of the Upper Alimentary and Respiratory Tracts in Rats

Eva Tydén, Hans Tjälve and Pia Larsson1

Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden

Received April 28, 2004; accepted July 7, 2004

Whole-body low-temperature radioluminography of 3H-2,6-xylidine in rats indicates that the nonmetabolized substance, which is a volatile and fat-soluble compound, is distributed throughout the body and accumulates in adipose tissues, e.g., in the abdominal and subcutaneous regions. Whole-body autoradiography with freeze-dried or solvent-extracted tissue sections as well as microautoradiography, which were used to trace tissues in the rats accumulating 2,6-xylidine metabolites, showed presence of tissue-bound 2,6-xylidine metabolites in the nasal olfactory mucosa and the mucosa of the upper alimentary and respiratory tracts. These tissues were found to have an in vitro capacity to bioactivate 2,6-xylidine. Our data indicate that 2,6-xylidine in vivo undergoes an in situ bioactivation in these extrahepatic tissues. Our results showed that the nasal olfactory mucosa had a much higher capacity than the other examined tissues to bioactivate 2,6-xylidine. Thus, the carcinogenic effect of 2,6-xylidine toward the nasal mucosa in rats is correlated with a high capacity of this tissue to bioactivate the compound.

Key Words: 2,6-xylidine; metabolic activation; nasal olfactory mucosa; alimentary tract; respiratory tract; nasal cancer.


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