Gomes-Carneiro M R, Dias Daniela M M, Paumgartten Francisco J R
Laboratory of Environmental Toxicology, Department of Biological Sciences, National School of Public Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-361, Brazil.
Food Chem Toxicol. 2006 Apr;44(4):522-7. doi: 10.1016/j.fct.2005.08.026. Epub 2005 Oct 11.
beta-Ionone (BIO) is a degraded (C(13)) sesquiterpenoid compound found in a variety of edible and aromatic plants. BIO and other ionone derivatives have been used in fragrance products and as flavoring food additives. In this study we investigated the mutagenic and antimutagenic activities of BIO using the Salmonella/microsome assay. Mutagenicity was evaluated by two tests with Salmonella typhimurium strains TA100, TA98, TA97a and TA1535, without and with addition of S9 mixture. A first assay was performed by the plate incorporation procedure and a confirmation test by the pre-incubation method. In either test, no increase in the number of his(+) revertant colonies over the negative (solvent) control values was noted with any of the four tester strains thereby indicating that BIO was not genotoxic in the Salmonella assay. Antimutagenic activity was investigated by testing (by the plate incorporation method) different non-toxic doses of BIO against one or more non-toxic doses of direct-acting (sodium azide: SA, 4-nitroquinoline-N-oxide: 4-NQNO, 2-nitrofluorene: 2-NF and nitro-o-phenylenediamine: NPD) as well as indirect-acting (cyclophosphamide: CP, benzo[a]pyrene: B[a]P, aflatoxin B1: AFB1, 2-aminoanthracene: 2-AA, and 2-aminofluorene: 2-AF) mutagens. BIO did not alter the effects of any direct-acting mutagen or B[a]P and 2-AF. Mutagenic effects of AFB1 and CP, however, were markedly and dose-dependently antagonized by BIO. It has been reported that, in the rat liver, activation of B[a]P and 2-AF depend on CYP1A1 activity, and that CYP2B subfamily is involved in the metabolic activation of CP and AFB1. It has also been described that BIO is a potent inhibitor of CYP2B1/2 and a weaker inhibitor of CYP1A1. Therefore, antagonism of CP-and AFB1-induced mutagenic effects by BIO could have been mediated-at least in part-by the inhibition of CYP2B enzymes.
β-紫罗兰酮(BIO)是一种降解的(C(13))倍半萜类化合物,存在于多种可食用和芳香植物中。BIO和其他紫罗兰酮衍生物已用于香料产品和作为食品调味添加剂。在本研究中,我们使用沙门氏菌/微粒体试验研究了BIO的致突变和抗突变活性。通过对鼠伤寒沙门氏菌菌株TA100、TA98、TA97a和TA1535进行两项试验来评估致突变性,试验分别在不添加和添加S9混合物的情况下进行。第一次试验通过平板掺入法进行,确认试验通过预孵育法进行。在任何一项试验中,四种测试菌株中的任何一种在his(+)回复突变菌落数量上均未超过阴性(溶剂)对照值,这表明BIO在沙门氏菌试验中没有遗传毒性。通过(平板掺入法)测试不同无毒剂量的BIO对一种或多种无毒剂量的直接作用诱变剂(叠氮化钠:SA、4-硝基喹啉-N-氧化物:4-NQNO、2-硝基芴:2-NF和硝基邻苯二胺:NPD)以及间接作用诱变剂(环磷酰胺:CP、苯并[a]芘:B[a]P、黄曲霉毒素B1:AFB1、2-氨基蒽:2-AA和2-氨基芴:2-AF)的抗突变活性。BIO没有改变任何直接作用诱变剂或B[a]P和2-AF的作用。然而,BIO显著且剂量依赖性地拮抗了AFB1和CP的诱变作用。据报道,在大鼠肝脏中,B[a]P和2-AF的活化依赖于CYP1A1活性,并且CYP2B亚家族参与CP和AFB1的代谢活化。还描述了BIO是CYP2B1/2的强效抑制剂和CYP1A1的较弱抑制剂。因此,BIO对CP和AFB1诱导的诱变作用的拮抗作用可能至少部分是通过抑制CYP2B酶介导的。