title: Effect of dietary casein levels on activation of promutagens in the spiral Salmonella mutagenicity assay. I. Studies with noninduced rat liver S9.
abstract: Xenobiotic metabolism can be influenced by various nutritional factors, including protein. In the present study, we have examined the effect of dietary protein (casein) levels on the ability of rat liver S9 to activate the promutagens aflatoxin B1 (AFB), 2-aminoanthracene (2AN) and benzo[a]pyrene (BAP) in strain TA98 using the spiral Salmonella mutagenicity assay. S9s were derived from individual male F344 rats fed for 6 weeks on semisynthetic diets containing 8%, 12% or 22% methionine-supplemented casein as the sole source of protein (diets were made isocaloric by adjusting the corn starch content). Rats were housed in large, raised-bed cages by groups of three per diet. S9 activation mixtures were prepared at 5 mg of S9 protein/ml of S9 mix. Slopes from the linear portions of the mutagenicity dose-response curves were analyzed by ANOVA comparisons. Assays used to elucidate the phase I activities of microsomal preparations were cytochrome P450 content, cytochrome-c reductase activity, flavin-containing monooxygenase activity, 7-ethoxyresorufin O-deethylation (EROD) activity, N-demethylation of benzphetamine and para-nitrophenol O-deethylation. Phase II activities in cytosolic preparations were assayed by estimation of glutathione (GSH) content and glutathione S-transferase activity through metabolism of 1-chloro-2,4-dinitrobenzene (CDNB). Increased levels of dietary casein increased liver wet weights and decreased the ability of the S9 to activate 2AN. Dietary casein levels did not influence the S9-mediated activation of BAP; and consistent but nonsignificant increases in activation of AFB were produced by S9 from animals fed the 22% casein diet. The phase I and phase II activities measured here were not altered significantly by dietary casein levels; thus, other, more specific enzymatic activities may account for the mutagenesis data. These results illustrate the complex interaction between dietary levels of casein and promutagen activation mechanisms, which prevents drawing broad generalizations regarding the influence of dietary casein levels on the capacity of hepatic S9s to activate promutagens.
authors.affiliation: Department of Toxicology, North Carolina State University, Raleigh 27695, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Woodall
authors.forename: W C
authors.initials: WC
authors.lastname: Dauterman
authors.forename: D M
authors.initials: DM
authors.lastname: DeMarini
mesh_terms: D016604:Aflatoxin B1 / Q000493:pharmacokinetics; D000818:Animals; D000873:Anthracenes / Q000493:pharmacokinetics; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics; D001711:Biotransformation; D001835:Body Weight; D002364:Caseins / Q000008:administration & dosage / Q000378:metabolism*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics*; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D012475:Salmonella / Q000235:genetics*
chemical_list: D000873:Anthracenes; D002364:Caseins; D004044:Dietary Proteins; D004798:Enzymes; D009153:Mutagens; D001564:Benzo(a)pyrene; C006593:2-anthramine; D016604:Aflatoxin B1