Role of metabolic polymorphisms NAT2 and CYP1A2 on urinary mutagenicity after a pan-fried hamburger meal

Abstract

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.