Absorption of Carcinogens into the Thoracic Duct Lymph of the Rat: Aminostilbene Derivatives and 3-Methylcholanthrene

Abstract

1. Highly ³H-labelled trans- and cis-dimethylaminostilbene and dimethyl -aminobibenzyl (22±5 μmol/kg), as well as 3-methylcholanthrene (18±7 μmol/kg), were administered orally to female rats with cannulated thoracic ducts and the labelled lymph constituents analysed by radio-g.l.c. and/or radio-t.l.c.

2. Only a small percentage of the aromatic dimethylamines appeared in lymph (03±2±7% of the dose in 24 h); several metabolites were identified. Of the administered methylcholanthrene 9% was recovered from lymph.

3. From the metabolite pattern it is concluded that the labelled substances recovered from thoracic duct lymph primarily originate from intestinal absorption, the metabolites being part of the enterohepatic circulation.

4. Lipid solubility appears to be a major prerequisite, but specific structural requirements contribute in determining the extent to which compounds enter the organism by way of the intestinal lymphatics.

5. Administered dimethylamino compounds and their metabolites in the enterohepatic circulation are almost entirely conveyed by the portal system into the liver following absorption. Direct distribution via the intestinal lymph, by-passing the liver, therefore may not influence the metabolism and the concentration in peripheral tissues of lipophilic derivatives. It may play a role, however, in case of carcinogenic aromatic hydrocarbons.