Kuroki T, Bartsch H
Cancer Lett. 1979 Feb;6(2):67-72. doi: 10.1016/s0304-3835(79)80002-6.
Mutagenicity of 4 N- and O-acyl derivatives of N-hydroxy-2-aminofluorene (acyl: acetyl or myristoyl residue) was examined in V79 Chinese hamster cells in the absence of a metabolic activation system. N-Myristoyloxy-N-acetyl-2-aminofluorene (N-MyO-AAF) was toxic and weakly mutagenic, inducing 8-azaguanine-resistant (AZAr) mutants in V79 Chinese hamster cells in a concentration-dependent fashion; while N-acetoxy-N-myristoyl-2-aminofluorene (N-AcO-MyAF) and N-myristoyloxy-N-myristoyl-2-aminofluorene (N-MyO-MyAF) were neither cytotoxic nor mutagenic. Under the same conditions, N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) was highly toxic and mutagenic. Neither of the 2 N-myristoyloxy derivatives was mutagenic in Salmonella typhimurium. These esters have been reported to produce local tumours at the site of their injection in rats, bo be electrophilic towards methionine, and to induce unscheduled DNA synthesis in cultured human fibroblasts. In view of the fact that some of the esters were mutagenic in neither S. typhimurium nor V79 Chinese hamster cells, our findings emphasize the need for multiple short-term tests in predicting potential carcinogenic activity of chemicals.
在无代谢活化系统的条件下，研究了N-羟基-2-氨基芴的4种N-和O-酰基衍生物（酰基：乙酰基或肉豆蔻酰基残基）在V79中国仓鼠细胞中的致突变性。N-肉豆蔻酰氧基-N-乙酰基-2-氨基芴（N-MyO-AAF）具有毒性且致突变性较弱，以浓度依赖的方式在V79中国仓鼠细胞中诱导8-氮杂鸟嘌呤抗性（AZAr）突变体；而N-乙酰氧基-N-肉豆蔻酰基-2-氨基芴（N-AcO-MyAF）和N-肉豆蔻酰氧基-N-肉豆蔻酰基-2-氨基芴（N-MyO-MyAF）既无细胞毒性也无致突变性。在相同条件下，N-乙酰氧基-N-乙酰基-2-氨基芴（N-AcO-AAF）具有高度毒性和致突变性。这2种N-肉豆蔻酰氧基衍生物在鼠伤寒沙门氏菌中均无致突变性。据报道，这些酯类在大鼠注射部位可产生局部肿瘤，对甲硫氨酸具有亲电性，并能在培养的人成纤维细胞中诱导DNA的非预定合成。鉴于部分酯类在鼠伤寒沙门氏菌和V79中国仓鼠细胞中均无致突变性，我们的研究结果强调了在预测化学物质潜在致癌活性时进行多种短期试验的必要性。
