Studies of the absorption and enterohepatic circulation of 7,12-dimethylbenz[a]anthracene in the rat.
This study was undertaken to examine intraluminal factors which might alter the bioavailability of an orally ingested hydrocarbon carcinogen, 7,12-dimethylbenz[a]anthracene, and to assess the extent of its enterohepatic circulation. Rats with biliary and duodenal fistulae were administered radiolabelled hydrocarbon dissolved in olive oil, safflower oil, or medium-chain triglyceride only or with exogenous bile. Subsequent biliary excretion and plasma levels of radiolabel were monitored. Luminal bile significantly enhanced biliary recovery of radiolabel following instillation in both long-chain triglyceride vehicles, but did not affect the recovery from the medium-chain oil. In the presence of luminal bile, plasma levels and biliary recovery of radiolabel using the medium-chain triglyceride were significantly less than with either long-chain triglyceride. Following intraduodenal infusions of the radiolabelled biliary products of the carcinogen, 33% of the administered radiolabel was subsequently re-excreted in the bile within 24 h. This study, therefore, demonstrates that, while bile is not absolutely necessary for the uptake of this orally ingested hydrocarbon carcinogen, it significantly facilitates absorption from a long-chain triglyceride vehicle. Under physiological conditions, a long-chain triglyceride vehicle will provide greater systemic availability than a medium-chain vehicle for the hydrocarbon, which then undergoes extensive biliary excretion and recycling.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D001652:Bile Ducts / Q000502:physiology; D004764:Enterohepatic Circulation; D007408:Intestinal Absorption; D008297:Male; D011083:Polycyclic Compounds / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001551:Benz(a)Anthracenes; D011083:Polycyclic Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene