Role of the lymphatic system in the transport of absorbed 7,12-dimethylbenzanthracene in the rat.

To determine the role of the intestinal lymphatic system in the absorption of a polycyclic aromatic hydrocarbon, 7,12-dimethylbenzanthracene, a radiolabeled preparation of the compound was given by intraduodenal infusion to rats in doses of 10 micrograms, 10 mg and 20 mg in olive oil solution. The hydrocarbon appeared to be absorbed from the intestine in a fractional manner, ca. 20% of the administered radioactivity being recovered totally in bile and intestinal lymph in 24 hr at all three dose levels. Biliary radiolabel accounted for 75-82% of combined recovery of radioactivity in bile and lymph with all three doses. The recovery of significant amounts of radiolabel in bile before the appearance of isotope in lymph, together with the fact that the biliary radiolabel greatly exceeded at all times the lymphatic recovery of isotope, suggests that an alternative pathway, presumably the portal venous route, is of major importance in the transport of the absorbed hydrocarbon.

Similar bioavailability and lymphatic transport of benzo(a)pyrene when administered to rats in different amounts of dietary fat.

This study assessed the effect of concomitant lipid absorption on the bioavailability and lymphatic transport of benzo(a)pyrene (BP), a carcinogenic polycyclic aromatic hydrocarbon (PAH). Conscious, male Sprague-Dawley rats, equipped with biliary and mesenteric lymphatic catheters received intraduodenally a dose of 0.4 mumoles 3H-labeled BP completely dissolved in either 50 mumoles or 500 mumoles of olive oil. Diversion of mesenteric lymph allowed biliary and urinary excretion of 3H to be used as an indirect measurement of relative 3H portal transport. Total radiolabel recovered in a 24-hr period in each group was 20.0 +/- 2.6% of the 3H dose given in 50 mumoles of oil, and 17.0 +/- 1.0% of the 3H dose administered in 500 mumoles of oil. In animals receiving the low-fat test meal, 79.4 +/- 1.4% of the recovered radiolabel was found in bile; the corresponding value for the high fat dose was 78.5 +/- 2.6%. Thus a tenfold variation in the mass of the carrier vehicle (triglyceride oil) did not significantly effect the disposition of BP, and portal, not lymphatic transport, was the major route of post-absorptive transport. Although the chylomicrons produced from both fat doses were initially contaminated with BP, within 1-1.5 hr the radioactivity in lymph began to drop such that by 3 hr in the animals fed high fat, the chylomicrons were essentially free of BP. These results show that the rat enterocyte quickly adapts to PAH-contaminated dietary fat, even during the assimilation of a single dose of fat. Presumably, during the post-absorptive synthesis of chylomicrons from pre-chylomicrons, BP is metabolized and removed from the triglyceride oil droplets.

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.

In vitro interaction of 7,12-dimethylbenz[a]anthracene and its biliary metabolites with dietary fiber.

This in vitro study examined the ability of various dietary fiber components to bind 7,12-dimethylbenz[a]anthracene (DMBA), a hydrocarbon carcinogen known to contaminate food. Bile salt solutions of DMBA were incubated with individual fiber materials under various conditions, and the degree of binding was assessed. Binding of DMBA from simple bile salt solution was greatest with delipidated bran greater than acid lignin greater than alpha-cellulose greater than unprocessed bran. Binding to acid lignin was slowly reversible, was constant within the pH range 4-8, and appeared independent of a bile salt-fiber interaction. Acid lignin bound DMBA from a mixed lipid-bile salt solution significantly, but less effectively than from pure bile salt solutions. DMBA biliary metabolites from Sprague-Dawley rats were bound less extensively to all the fiber materials than was the parent hydrocarbon, but following hydrolysis of the metabolites by beta-glucuronidase binding was significantly increased. These results indicate that there is considerable potential for dietary fiber to interact with DMBA and its metabolites in the lumen of the gastrointestinal tract, possibly influencing hydrocarbon carcinogen bioavailability.

Polycyclic hydrocarbon and polychlorinated biphenyl solubilization in aqueous solutions of mixed micelles.

To determine the physiochemical behavior of xenobiotic hydrocarbons in simulated intestinal content, we examined the partition of 7,12-dimethylbenzanthracene (DMBA), 3-methyl cholanthrene (MC), benzo(a)pyrene, and a polychlorinated biphenyl compound (PCB, Aroclor 1242) between an emulsified oil phase and a mixed micellar solution. In a mixed lipid-bile salt system, negligible amounts of hydrocarbon were present in aqueous solution below the critical micellar concentration (CMC) of sodium taurocholate. Once the CMC was obtained, the 4 hydrocarbons exhibited nearly identical partitions from the lipid into the micellar system which was enhanced by increased concentrations of bile salt, reduction of triglyceride concentration and the formation of mixed rather than pure bile salt micelles. The partition of DMBA and MC into micelles was optimized by long-chain monounsaturated oleic acid and monooleoylglycerol as compared to their octanoic or linoleic counterparts. Linoleic acid and monolinoleoylglycerol maximized the partition of PCB from the oil into the micellar phase. In a mixed micellar system excluding an oil phase and an excess of DMBA, a molar saturation ratio (mol hydrocarbon:mol bile salt) was calculated by regression analysis to be 0.162. This indicates that more than one molecule of hydrocarbon is solubilized per mixed micelle and that the aqueous solubilization of hydrocarbon may be attributed to true micellar solubilization.