Metabolic activation of 2,6-xylidine in the nasal olfactory mucosa and the mucosa of the upper alimentary and respiratory tracts in rats.
Whole-body low-temperature radioluminography of (3)H-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.
Tydén
Eva
E
Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden.
Tjälve
Hans
H
Larsson
Pia
P
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D004247:DNA / Q000378:metabolism; D005260:Female; D005612:Freeze Drying; D009061:Mouth Mucosa / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014915:Whole-Body Counting
D000814:Aniline Compounds; D011506:Proteins; C007766:2,6-xylidine; D004247:DNA