Abstract

Whole-body autoradiography of H-3-labeled aflatoxin B1 (AFB1) in adult C57BL mice pretreated with the glutathione (GSH)-depleting agent phorone showed accumulation of tissue-bound radioactivity in the nasal olfactory and respiratory mucosa, the mucosa of the nasopharyngeal duct, and the tracheal and esophageal mucosa, which was not seen in unpretreated adult mice. The altered distribution pictures induced by the phorone are probably related to decreased tissue levels of GSH. The AFB1 is likely to be bioactivated locally in the extrahepatic tissues; in nonpretreated mice the reactive AFB1 metabolite formed is probably scavenged by GSH vis the action of glutathione-S-transferase, whereas in the mice with depleted GSH levels a binding to tissue macromolecules will instead take place. The mechanism indicated above is supported by results of in vitro experiments in which the nasal olfactory mucosa and the esophageal mucosa were shown to have a capacity to form tissue-bound H-3-AFB1 metabolites. This formation was decreased when the incubations were performed in the presence of GSH. In addition, the treatments of mice with phorone were shown to induce a strong GSH depletion in the nasal olfactory mucosa and the esophageal mucosa.In autoradiographic studies performed with 1- and 5-day-old infant mice a marked localization of bound H-3-AFB1 metabolites was found in the nasal olfactory mucosa, and in the 5-day-old infant there was also a labeling of the mucosa of the nasopharyngeal duct, the pharyngeal and esophageal mucosa, and the tracheal mucosa. Experiments in vitro with the nasal olfactory mucosa of 5-day-old infants demonstrated a marked binding of H-3-AFB1 metabolites in this tissue. Incubations together with GSH decreased this binding, although the inhibition was less marked than in the adult animal. The in vivo accumulation of bound AFB1 metabolites in the extrahepatic tissues of the infant mice may be related to low glutathione-S-transferase (GST) activity in the tissues of the young animals. In addition, some extrahepatic tissues may have a considerable capacity to bioactivate the AFB1 at early age.Autoradiography of H-3-AFB1 in pregnant mice showed a labeling of the fetal nasal olfactory mucosa at day 18 but not at day 14 of gestation. This indicates that AFB1-bioactivating enzymes develop in the fetal nasal olfactory mucosa in late gestation.

Published in

Cancer Research
1992, Volume: 52, number: 5, pages: 1267-1277
Publisher: AMER ASSOC CANCER RESEARCH

SLU Authors

• Larsson, Pia

  • Department of Pharmacology and Toxicology, Swedish University of Agricultural Sciences
    

• Tjälve, Hans

  • Department of Pharmacology and Toxicology, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Pharmacology and Toxicology


Permanent link to this page (URI)

https://res.slu.se/id/publ/40219