Extrahepatic bioactivation of aflatoxin B1 in fetal, infant and adult rats.
Whole-body autoradiography of 3H-labelled aflatoxin B1 (3H-AFB1) in female non-pregnant adult and infant Sprague-Dawley rats showed retention of tissue-bound radioactivity, in addition to the liver, in the mucosa and some glands in the nose, and in the mucosa of the nasopharynx, trachea, bronchioles, colon and caecum. The extrahepatic binding was most pronounced in the infant rats. In a rat pretreated with the glutathione (GSH)-depleting agent phorone, bound labelling was also seen in the superficial part of the mucosa of the glandular stomach. Autoradiography of 3H-AFB1 in pregnant rats showed a marked localization of bound AFB1-metabolites in the fetal nasal olfactory and tracheal mucosa. In vitro experiments demonstrated that the nasal olfactory mucosa had a much higher capacity than the liver to form AFB1-metabolites which bound to DNA and protein. The bioactivation was observed both pre- and post-natally and increased with age. Bioactivation was found also in the caecum, the colon and the lateral nasal gland (Steno's gland), but not in the small intestine, oesophagus or Harderian gland. Our results indicated that glutathione-S transferase activity catalysing the AFB1-8,9-epoxide GSH-conjugation was present in the nasal olfactory mucosa and liver at all pre- and post-natal ages examined. Several of the extrahepatic tissues able to bioactivate AFB1 have been reported to be targets for the carcinogenicity of the substance. Our results indicate that the extrahepatic carcinogenicity of AFB1 is correlated to a local bioactivation in the sensitive tissues.
Larsson
P
P
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
Tjälve
H
H
D016604:Aflatoxin B1 / Q000493:pharmacokinetics*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001345:Autoradiography; D001711:Biotransformation; D001980:Bronchi / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology; D008099:Liver / Q000196:embryology / Q000378:metabolism; D009092:Mucous Membrane / Q000196:embryology / Q000378:metabolism; D009297:Nasal Mucosa / Q000196:embryology / Q000378:metabolism; D009305:Nasopharynx / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000196:embryology / Q000378:metabolism; D014316:Tritium
D007659:Ketones; D014316:Tritium; C018637:phorone; D004247:DNA; D016604:Aflatoxin B1; D005978:Glutathione