Department of Environmental Science and Policy, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
Regul Toxicol Pharmacol. 2019 Jul;105:36-41. doi: 10.1016/j.yrtph.2019.03.017. Epub 2019 Mar 29.
Food-borne alkenylbenzenes are potential risks for human health because they are known to induce liver tumors in rodent bioassays at high dose levels. This carcinogenicity is ascribed to the conversion of their 1'-hydroxymetabolites to the ultimate DNA reactive and carcinogenic 1'-sulfoxymetabolites. The aim of this study was to investigate the in vitro genotoxicity of some botanical extracts used as Plant Food Supplements (PFS) and to compare it with the individual substances, estragole, safrole and their 1'-hydroxy-derivative activity. The genotoxicity of the PFSs was evaluated in HepG2 cell line by comet and micronucleus assays. Unlike the 1'-hydroxy derivatives, PFS extracts and parent alkenylbenzenes did not show genotoxicity at any of the tested concentrations. The sulfotransferase inhibitor pentachlorophenol (PCP) reduced the 1'-hydroxy compound-induced response in the comet and micronucleus assays, thus confirming that the formation of sulfoxy-metabolites is essential for inducing genotoxic effects. When the cells were treated with hydroxylated alkenylbenzenes in the presence of PFSs, a reduction in genotoxic activity of synthetic compounds was observed.
食源性烯基苯是对人类健康的潜在风险,因为它们已知在高剂量水平的啮齿动物生物测定中会诱导肝肿瘤。这种致癌性归因于它们的 1'-羟代谢物转化为最终的 DNA 反应性和致癌的 1'-亚砜代谢物。本研究的目的是研究一些用作植物食品补充剂 (PFS) 的植物提取物的体外遗传毒性,并将其与个体物质,黄樟素、沙菲醇及其 1'-羟基衍生物的活性进行比较。通过彗星和微核试验评估 PFS 在 HepG2 细胞系中的遗传毒性。与 1'-羟基衍生物不同,PFS 提取物和母体烯基苯在任何测试浓度下均未显示出遗传毒性。磺基转移酶抑制剂五氯苯酚 (PCP) 降低了彗星和微核试验中 1'-羟基化合物诱导的反应,从而证实了亚砜代谢物的形成对于诱导遗传毒性效应是必不可少的。当细胞在用 PFS 处理羟化烯基苯时,观察到合成化合物的遗传毒性活性降低。