Skipper P L, Tannenbaum S R, Thilly W G, Furth E E, Bishop W W
Cancer Res. 1980 Dec;40(12):4704-8.
A series of hydroxamic acids (aceto-, propiono-, benzo-, and p-nitrobenzo-) and seven derivatives of these were examined for biological activity using Salmonella typhimurium. Acylation to yield O-acetyl and O-benzoyl derivatives markedly enhanced toxic properties and was necessary for mutagenic activity for all but p-nitrobenzohydroxamic acid. The dose necessary to produce a minimum significant mutagenic response varied from 21 microM for O-benzoyl benzohydroxamate to 430 microM for O-acetyl acetohydroxamate. These two compounds were also tested with human lymphoblasts to which they were toxic at 100 microM but not mutagenic. O-Acetyl benzohydroxamate, a mutagen, was prepared wih a 14C label in the carbonyl carbon atom of the benzoyl group and was shown to form an adduct in vitro with DNA and polyguanylic acid. The level of binding was 1 mol of 14C per 5 X 10(4) mol of DNA phosphate and 1 mol of 14C per 10(5) mol of polyguanylic acid phosphate.
使用鼠伤寒沙门氏菌对一系列异羟肟酸（乙酰基、丙酰基、苯甲酰基和对硝基苯甲酰基）及其七种衍生物进行了生物活性检测。酰化生成O - 乙酰基和O - 苯甲酰基衍生物显著增强了毒性，且除对硝基苯异羟肟酸外，对所有物质的诱变活性都是必需的。产生最小显著诱变反应所需的剂量从O - 苯甲酰基苯异羟肟酸的21微摩尔到O - 乙酰基乙酰异羟肟酸的430微摩尔不等。还用人淋巴细胞对这两种化合物进行了测试，它们在100微摩尔时对人淋巴细胞有毒性，但不具有诱变性。O - 乙酰基苯异羟肟酸是一种诱变剂，在苯甲酰基的羰基碳原子上用14C标记制备而成，并且显示在体外能与DNA和聚鸟苷酸形成加合物。结合水平为每5×10(4)摩尔DNA磷酸有1摩尔14C，每10(5)摩尔聚鸟苷酸磷酸有1摩尔14C。
