Peterson Lisa A, Cummings Meredith E, Chan Jacqueline Y, Vu Choua C, Matter Brock A
Division of Environmental Health Sciences and the Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Chem Res Toxicol. 2006 Sep;19(9):1138-41. doi: 10.1021/tx060111x.
The hepatocarcinogen and toxicant furan requires metabolic activation to elicit its toxic effects. The available experimental evidence indicates that the overall metabolism of furan is initiated via cytochrome P450 catalyzed oxidation to cis-2-butene-1,4-dial. This alpha,beta-unsaturated dialdehyde reacts in vitro with protein and DNA nucleophiles. To determine if this compound is an in vivo intermediate in the metabolism of furan, rats were treated with either [(12)C(4)]furan or [(13)C(4)]furan, and urine was collected for 24 h. Capillary LC/MS/MS analysis of the urine indicated that one of the metabolites was a monoglutathione conjugate of cis-2-butene-1,4-dial. These results indicate that glutathione conjugation of the reactive metabolite of furan occurs in vivo. This metabolite may serve as a useful marker for furan exposure and metabolism in risk assessment studies.
肝癌致癌物及毒物呋喃需要代谢活化才能引发其毒性作用。现有实验证据表明，呋喃的整体代谢是通过细胞色素P450催化氧化开始，生成顺式-2-丁烯-1,4-二醛。这种α,β-不饱和二醛在体外与蛋白质和DNA亲核试剂发生反应。为了确定该化合物是否为呋喃代谢过程中的体内中间体，给大鼠分别注射[(12)C(4)]呋喃或[(13)C(4)]呋喃，并收集24小时尿液。尿液的毛细管液相色谱/串联质谱分析表明，其中一种代谢产物是顺式-2-丁烯-1,4-二醛的单谷胱甘肽共轭物。这些结果表明，呋喃的活性代谢产物在体内会发生谷胱甘肽共轭反应。这种代谢产物可能作为风险评估研究中呋喃暴露和代谢的有用标志物。
