Venkat J A, Shami S, Davis K, Nayak M, Plimmer J R, Pfeil R, Nair P P
Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, MD 20705.
Environ Mol Mutagen. 1995;25(1):67-76. doi: 10.1002/em.2850250110.
The genotoxic activities of 47 pesticides were determined using a modified SOS microplate assay in which the induction of beta-galactosidase in E. coli PQ37 was used as a quantitative measure of genotoxic activity. The results were compared with those obtained with anethole, curcumin, and capsaicin, a few examples of naturally occurring compounds present in foods. The assays were conducted with pesticides dissolved either in a suitable solvent, such as 10% DMSO in physiological saline or dispersed in sodium taurocholate micelles, to simulate conditions in the small intestine from where these substances are normally absorbed from the diet. 4-Nitroquinoline oxide (4-NQO) served as the reference standard of a direct acting mutagen. In micellar form, 4-NQO and 25 of the 47 pesticides tested showed significantly higher genotoxic activities than when they were tested in an organic solvent. In micellar form the SOS inducing potency of 4-NQO was almost twice as high as in 10% DMSO in physiological saline. In taurocholate micelles, the five most active compounds had activities in the range of 1,234-3,765 units/mumol and in the order of decreasing activities they were ranked as follows: malathion > dichlorvos > lindane > chlordane > endrin. They were significantly less active than 4-NQO (less than 40%). In micellar solution the naturally occurring compounds, anethole, curcumin, and capsaicin gave activities of 4,594, 928, and 809 units/mumol, respectively. These studies show that genotoxicity may depend upon the environment in which cells are exposed to these potential genotoxins. It appears that testing of the more hydrophobic compounds, both synthetic and naturally occurring, are needed.
采用改良的SOS微孔板试验测定了47种农药的遗传毒性活性,该试验以大肠杆菌PQ37中β-半乳糖苷酶的诱导作为遗传毒性活性的定量指标。将结果与用茴香脑、姜黄素和辣椒素(食品中天然存在的几种化合物)所获得的结果进行了比较。试验采用溶解在合适溶剂(如生理盐水中10%的二甲基亚砜)中的农药进行,或将农药分散在牛磺胆酸钠胶束中进行,以模拟这些物质通常从饮食中吸收的小肠环境。4-硝基喹啉氧化物(4-NQO)用作直接作用诱变剂的参考标准。以胶束形式存在时,4-NQO和所测试的47种农药中的25种显示出比在有机溶剂中测试时显著更高的遗传毒性活性。以胶束形式存在时,4-NQO的SOS诱导能力几乎是在生理盐水中10%二甲基亚砜中的两倍。在牛磺胆酸钠胶束中,五种活性最高的化合物的活性范围为1234 - 3765单位/微摩尔,按活性递减顺序排列如下:马拉硫磷>敌敌畏>林丹>氯丹>异狄氏剂。它们的活性明显低于4-NQO(低于40%)。在胶束溶液中,天然存在的化合物茴香脑、姜黄素和辣椒素的活性分别为4594、928和809单位/微摩尔。这些研究表明,遗传毒性可能取决于细胞暴露于这些潜在遗传毒素的环境。似乎需要对更多疏水性化合物(包括合成的和天然存在的)进行测试。