Pavanello S, Simioli P, Mastrangelo G, Lupi S, Gabbani G, Gregorio P, Clonfero E
Section of Occupational Health, Department of Environmental Medicine and Public Health, University of Padova, Italy.
Food Chem Toxicol. 2002 Aug;40(8):1139-44. doi: 10.1016/s0278-6915(02)00038-8.
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.
在本研究中，采用表型分析方法，研究了代谢多态性NAT2和CYP1A2对50名受试者食用煎制汉堡包后S9介导的尿液诱变性的影响，尿液诱变性通过沙门氏菌菌株YG1024检测。所有50份餐后样本均具有明显的诱变性，而餐前样本则无（能够使自发回复突变体数量翻倍的尿液样本数量分别为50和0）。CYP1A2对尿液诱变性有正向影响：CYP1A2活性升高会增加餐后尿液诱变剂水平（7小时最低诱变剂量（MMD）/摄入量分别为1.16±0.91和1.72±1.19），尤其是在NAT2慢乙酰化者中（7小时MMD/摄入量分别为2.18±1.33和0.90±0.54，Mann-Whitney U检验，P<0.05）。NAT2快乙酰化者餐后尿液诱变性低于慢乙酰化者（7小时MMD/摄入量分别为1.41±1.02和1.77±2.45），如果慢乙酰化者是CYP1A2广泛代谢者，差异则更明显（7小时MMD/摄入量分别为1.41±1.02和2.18±1.33），但差异未达到统计学意义。总之，本研究表明，CYP1A2和NAT2活性会影响食用富含杂环胺的煎制汉堡包后尿液诱变剂的存在，从而影响其潜在的基因毒性风险。
