Metabolism of aflatoxin B1 in the bovine olfactory mucosa

Carcinomas of the ethmoidal region of the nose are observedrelatively frequently in cattle in several countries in tropicaland subtropical latitudes. Viruses have been implicated as causativeagents, but it has been observed that affected animals sometimessuffer from aflatoxicosis, and a role of aflatoxin B₁ (AFB₁)in the aetiology has also been proposed. We have examined whetherthe bovine nasal olfactory mucosa has a capacity to metabolizeAFB₁. The contents of cytochrome P–450 and cytochromeb₅, and the NADPH cytochrome c reductase activity in the nasalolfactory mucosa have also been determined. Comparative experimentshave been performed with the liver. Incubations with ³H-labelledAFB₁ showed that the nasal olfactory mucosa has a much highercapacity than the liver to form lipid-soluble, water-solubleand tissue-bound AFB₁-metabolites. High-resolution microautoradiographyshowed a strong localization of tissue-bound metabolites inthe sustentacular cells in the apical portion of the olfactorysurface epithelium and in Bowman's glands in the olfactory laminapropria mucosae. Especially in the sustentacular cells the labellingwas preferentially located in the nuclei of the cells. Liquidchromatography of chloroform extracts of the nasal olfactorymucosa and the liver incubated with ³H-AFB₁ showed formationof several metabolites. The dominating peak in both tissueswas aflatoxin M₁ (AFM₁). However, the amount of AFM₁ was higherin the nasal olfactory mucosa than in the liver, and the amountsand proportions of several other metabolites also differed markedlybetween the two tissues. The level of cytochrome P-450 in thenasal olfactory mucosa was found to be about one quarter ofthat in the liver, but the NADPH cytochrome c reductase activitywas much higher in the nasal olfactory mucosa than in the liver.In addition, the cytochrome b₅: cytochrome P-450 ratio was higherin the nasal olfactory mucosa than in the liver. The highermetabolism of AFB₁ in the nasal olfactory mucosa than in theliver may be related to differences in the cytochrome P-450isoenzyme profile. In addition, the microsomal electron transportto cytochrome P-450 may be facilitated by the high reductase:cytochrome P–450 ratio and the high cytochrome b₅: cytochromeP–450 ratio in the nasal olfactory mucosa. It is consideredthat the results of the present study strengthen the hypothesisthat exposure of AFB₁-contaminated feed may be an importantaetiological factor in the development of nasal tumours in cattle.