The effects of high fat and high cholesterol diets on the disposition of Benzo(a)pyrene in the gut

Abstract

The possible interactions of high dietary levels of fat (HF) or fat + cholesterol (HC) with the lipid-soluble carcinogen benzo(a)pyrene (BP) have been investigated in the male guinea pig. Bile was the major route of elimination of ["^C]BP (25pCl i.v.) in normal animals, with a mean of 33% + a standard deviation of 13% of the dose excreted within 4h. Animals fed HF or HC diets showed a similar biliary elimination (27+13% and 37+15% respectively). However, the pattern of biliary metabolites was altered, such that a greater proportion of the recovered dose was present as BP dihydrodiols and their conjugates in HF and HC groups. The most marked increase was found in the 4,5-dihydrodiol glucuronide fraction, which increased from 2.4% of the C in bile to 13.5% and 11.6% in HF and HC groups respectively (p<0.01). Incubation of a number of BP metabolites with pure cultures of intestinal bacteria or guinea pig caecal contents resulted in hydrolysis of conjugated metabolites, particularly glucuronides, but primary oxidative metabolites of BP were stable to degradation. Cytochrome P450 and aryl hydrocarbon hydroxylase (AHH) were present in liver and small intestinal mucosa from normal animals, but were undetectable in colon and rectum. The administration of HF and HC diets, and/or repeated doses of BP (3mg/kg p.o. twice weekly for 3 weeks prior to sacrifice), did not increase these levels in colon and rectum. The administration of [^H]BP (2-4mCi p.o.) resulted in low levels of ^ H binding to DNA of the gut mucosa in normal animals, much of which could be accounted for by tritium exchange. The feeding of HF and HC diets did not increase this binding. Therefore the administration of HF and HC diets increased the metabolism of BP via the dihydrodiol pathways. Conjugates of these metabolites are hydrolysed by intestinal bacteria, and the aglycones appear stable to further degradation. However, due to the low and apparently non-inducible levels of AHH in guinea pig colon and rectum, there was no observed increase in DNA binding in these tissues.

More information

Identifiers

Catalogue record

Export record