Systematic modulation by human diet levels of dietary fibre and beef on metabolism and disposition of benzo[a]pyrene in the gastrointestinal tract of Fischer F344 rats
Groups of male Fischer F344 rats isocalorically consuming cooked, low-fat human diets were given magnetic polyethyleneimine (PEI) microcapsules and [14C]benzo[a]pyrene (B[a]P) by gavage in order to determine the effects of 3-fold changes in levels of dietary fibre non-starch polysaccharide (NSP) and beef protein during gastrointestinal transit on microcapsule trapping and assaciated parameters. Tdal 14C trapped by microcapsules during 70 h was decreased by fibre and increased by beef with significant effects (P = 0.03) for dietary mass ratio beef/fibre and compared to controls eating chow. Total B[a]P excreted in faeces and the ratio for faeces/urine were increased by fibre and not by beef; the distribution of B[a]P metabolites between liquid and solids of faeces was increased by both factors but there was a net decrease by fibre when allowing for its influence on faecal mass. The distribution of binding between microcapsules and faecal solids was incrrased significantly by beef, but fibre had no effect when mass-normalized. B[a]P metabolites were extracted from microcapsules by methanol—ammonia and HPLC assay showed mainly benzo[a]pyrene-3,6-dione (B[a]P 3,6-dione), benzo[a]pyrene-1,6-dione (B[a]P 1,6-dione), an unidentified metabolite and substances consistent with tetraols; the beef (P = 0.02) and beef/fibre ratio (P = 0.01) significantly increased B[a]P-l,6-dione trapped and released. In vitro, B[a]P 3,6-semidione (dione reduced form) was bound by PEI microcapsules; the extent of extraction/hydrolysis was much lower than for B[a]P 3,6-dione or B[a]P 7,8-diol 9.10-epoxide. Urinary excretion of B[a]P metabolites was decreased by fibre but not by beef. Nearly all the above parameters were different in a control group consuming rat chow. Taken together, these results are consistent with the following conclusions; (i) dietary fibre NSP overall decreases the availability of B[a]P metabolites to contact microcapsules and intestinal mucm through static bulking rather than absorption; (ii) beef protein increases binding to microcapsules, and enhances free radical activation of B[a]P to its 6-yl radical form; (iii) a systematic set of concordant relationships for B[a]P dispsition were found between faecal solids, faecal liquids, microcapsules and urine; and (iv) rat chow produced effects quite unrepresentative of the range for human diets prepared to be in the norm for human use. Endogenous UV-absorbing substances trapped by micro- capsules or excreted in urine were also altered by dietary beef levels and were different from those of chow-consuming anunals. it is generally concluded that human diets can and should be used in studying carcinogen metabolism and disposition.