Role of metabolic polymorphisms NAT2 and CYP1A2 on urinary mutagenicity after a pan-fried hamburger meal.
In this work the phenotyping approach was used to study the influence of metabolic polymorphisms NAT2 and CYP1A2 on S9-mediated urinary mutagenicity, detected with Salmonella strain YG1024, in 50 subjects after a meal of pan-fried hamburgers. All 50 post-meal samples, but not pre-meal ones, were clearly mutagenic (number of urine samples able to double number of spontaneous revertants was 50 to 0, respectively). CYP1A2 positively influences urinary mutagenicity: a rise in CYP1A2 activity increases levels of post-meal urinary mutagens (1.16+/-0.91 vs 1.72+/-1.19 7-h minimum mutagenic doses (MMDs)/intake), especially in NAT2 slow acetylators (2.18+/-1.33 vs 0.90+/-0.54 7-h MMDs/intake, Mann-Whitney U-test, P<0.05). NAT2 rapid acetylators exert lower post-meal urinary mutagenicity than slow ones (1.41+/-1.02 vs 1.77+/-2.45 7-h MMDs/intake) and even more if the latter are extensive CYP1A2 metabolizers (1.41+/-1.02 vs 2.18+/-1.33 7-h MMDs/intake), but the difference did not reach statistical significance. In conclusion, this study indicates that CYP1A2 and NAT2 activities influence the presence of urinary mutagens after a meal of pan-fried hamburger (rich in HHAs) and consequently their potential genotoxic risk.
Pavanello
S
S
Section of Occupational Health, Department of Environmental Medicine and Public Health, University of Padova, Italy. sofia.pavanello@unipd.it
Simioli
P
P
Mastrangelo
G
G
Lupi
S
S
Gabbani
G
G
Gregorio
P
P
Clonfero
E
E
D000328:Adult; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D015415:Biomarkers; D002417:Cattle; D003296:Cooking; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008461:Meat Products / Q000009:adverse effects*; D008875:Middle Aged; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000008:administration & dosage* / Q000032:analysis; D011110:Polymorphism, Genetic; D012475:Salmonella / Q000201:enzymology / Q000235:genetics; D014556:Urine / Q000737:chemistry
D015415:Biomarkers; D009153:Mutagens; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human