Activation of chemical carcinogens by cultured human fetal liver, esophagus and stomach.
Cultured fetal human stomach, esophagus and liver activated benzo[a]pyrene (BP), aflatoxin B1 (AFB) and certain N-nitrosamines into metabolites that bound to cellular DNA. When the 3 organs were compared the highest level of activity was observed in the stomach. The interindividual variation was 10-fold and the amount of carcinogen-DNA adducts did not correlate with the sex or age of the fetus. The reaction products between BP or AFB and cellular DNA were investigated in liver explants. The carcinogen-DNA adduct patterns were identical to those observed in adult human tissues; BPDEI-Gua being the major adduct formed by BP and 2,3-dihydro-2-(7'-guanyl)-3-hydroxy-AFB by AFB. The results indicate that fetal organs can metabolize those oncogenic compounds at an early stage of the development, and that the metabolic pathways and DNA adducts are quite similar to those in experimental animals in which the compounds are carcinogenic.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D046508:Culture Techniques; D004247:DNA / Q000378:metabolism; D004947:Esophagus / Q000196:embryology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D008099:Liver / Q000196:embryology*; D008297:Male; D009602:Nitrosamines / Q000378:metabolism; D011247:Pregnancy; D013270:Stomach / Q000196:embryology*
D000348:Aflatoxins; D001580:Benzopyrenes; D002273:Carcinogens; D009602:Nitrosamines; D001564:Benzo(a)pyrene; D004247:DNA; D016604:Aflatoxin B1