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ToxSci Advance Access published online on July 14, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh219
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received April 28, 2004
Accepted July 7, 2004

Biotransformation and Toxicokinetics

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 1, Hans Tjälve 1, Pia Larsson 1*

1 Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Box 7028, 750 07 Uppsala, Sweden

* To whom correspondence should be addressed. E-mail: Pia.Larsson{at}farmtox.slu.se.


  Abstract

Whole-body low-temperature radioluminography of 3H-2,6-xylidine in rats indicates that the non-metabolized 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 towards the nasal mucosa in rats is correlated to a high capacity of this tissue to bioactivate the compound.

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