title: Pilot study of free and conjugated urinary mutagenicity during consumption of pan-fried meats: possible modulation by cruciferous vegetables, glutathione S-transferase-M1, and N-acetyltransferase-2.
abstract: Epidemiological and experimental evidence indicates that consumption of fried meats in conjunction with certain genotypes of phase I and II metabolism genes poses an elevated risk for colorectal cancer. Parallel to this, the consumption of cruciferous vegetables is associated with a reduced risk of colon cancer. Therefore, we designed a 6-week pilot feeding study to evaluate the effect of these variables on urinary mutagenicity, which is a biomarker associated with fried-meat consumption. Eight subjects were fed fried meats daily for six weeks; four ate cruciferous vegetables, and four ate non-cruciferous vegetables. Urinary mutagenicity was evaluated in the presence of S9 in strain YG1024 of Salmonella, which is a frameshift strain that overproduces acetyltransferase. C18/methanol extracts of 24-h urines collected once each week were tested unhydrolyzed (free mutagenicity) and hydrolyzed (total mutagenicity); the difference between the two was the conjugated mutagenicity. Although not significant, the levels of conjugated urinary mutagenicity doubled among crucifera consumers and decreased to 30% of the initial levels among non-crucifera consumers, suggesting the possibility that crucifera may enhance the level of conjugated urinary mutagenicity resulting from consumption of fried meats. Such an effect would be consistent with the documented ability of cruciferous vegetables to induce phase II enzymes. The NAT2 rapid phenotype was significantly associated with approximately 2-fold increases in conjugated (p = 0.05) and total (p = 0.004) urinary mutagenicity relative to NAT2 slow subjects, consistent with the elevated risk confirmed by the NAT2 rapid phenotype for colorectal cancer among meat consumers. An approximately 2-fold increase in urinary mutagenicity among the GSTM1- subjects relative to the GSTM1+ subjects approached significance for free (p = 0.18) and total (p = 0.13) urinary mutagenicity. This is the first report on (a) the mutagenicity of hydrolyzed urine, which was consistently more mutagenic than unhydrolyzed urine; (b) the potential enhancement of conjugated urinary mutagenicity by crucifera; and (c) the association of the rapid NAT2 and possibly the GSTM1- phenotype with elevated levels of fried meat-associated urinary mutagenicity.
authors.affiliation: Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. demarini.david@epamail.epa.gov
authors.forename: D M
authors.initials: DM
authors.lastname: DeMarini
authors.forename: S B
authors.initials: SB
authors.lastname: Hastings
authors.forename: L R
authors.initials: LR
authors.lastname: Brooks
authors.forename: B T
authors.initials: BT
authors.lastname: Eischen
authors.forename: D A
authors.initials: DA
authors.lastname: Bell
authors.forename: M A
authors.initials: MA
authors.lastname: Watson
authors.forename: J S
authors.initials: JS
authors.lastname: Felton
authors.forename: R
authors.initials: R
authors.lastname: Sandler
authors.forename: L
authors.initials: L
authors.lastname: Kohlmeier
mesh_terms: D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D019607:Brassicaceae; D003296:Cooking; D004032:Diet; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008460:Meat; D008875:Middle Aged; D009152:Mutagenicity Tests; D009153:Mutagens / Q000032:analysis*; D010865:Pilot Projects; D014556:Urine / Q000737:chemistry*; D014675:Vegetables
chemical_list: D009153:Mutagens; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase