title: Dietary fibre, fat and beef modulation of colonic nuclear aberrations and microcapsule-trapped gastrointestinal metabolites of benzo[a]pyrene-treated C57/B6 mice consuming human diets.
abstract: Male C57/B6 mice were adapted to human diets of British origin that had 3-fold differences in either dietary fibre, fat or beef protein within the normal human range, and were then treated p.o. with 200 mg/kg benzo[a]pyrene (B[a]P) to induce colonic nuclear aberrations. [14C]B[a]P was included in the dose that followed 2 h after a gavage of magnetic PEI microcapsules. Untreated control groups were fed mouse chow or the baseline human diet which was low in all three dietary components (LLL). After the animals were killed at 24 h, large reductions (P less than 0.05) in colonic nuclear aberrations, and alterations to faecally excreted, microcapsule-trapped B[a]P metabolites were found for elevations of all three human diet components. Compared to untreated LLL control, B[a]P treatment gave an 8-fold increase in total nuclear aberrations, which was decreased 2- to 3-fold by increased fibre or fat. HPLC assay of B[a]P metabolites desorbed from microcapsules showed dietary fibre and beef protein to increase B[a]P diols and phenols but almost abolish B[a]P diones, consistent with a shift to enzymatic metabolism from non-specific oxidation. Increased fat considerably altered B[a]P metabolite disposition and microcapsule trapping, and comparison with microcapsules removed from colon contents indicated an altered enterohepatic circulation. Although it was not possible to attribute nuclear aberrations to individual B[a]P metabolites, a possible role of B[a]P diones seemed indicated, this being in line with previous microcapsule studies. These results show that microcapsules and human diets can be used in monitoring modulations of xenobiotic agents linked to mucosal chromosomal damage, with the eventual aim of human microcapsule biomonitoring.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: I K
authors.initials: IK
authors.lastname: O'Neill
authors.forename: M T
authors.initials: MT
authors.lastname: Goldberg
authors.forename: F
authors.initials: F
authors.lastname: el Ghissassi
authors.forename: M
authors.initials: M
authors.lastname: Rojas-Moreno
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D002250:Carbon Radioisotopes; D002417:Cattle; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002869:Chromosome Aberrations; D003106:Colon / Q000378:metabolism / Q000648:ultrastructure*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000235:genetics; D004249:DNA Damage; D004041:Dietary Fats / Q000378:metabolism*; D004043:Dietary Fiber / Q000378:metabolism*; D004339:Drug Compounding; D005243:Feces / Q000737:chemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008460:Meat / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D012307:Risk Factors
chemical_list: D002250:Carbon Radioisotopes; D004041:Dietary Fats; D004043:Dietary Fiber; D001564:Benzo(a)pyrene