Negishi T, Shiotani T, Fujikawa K, Hayatsu H
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Mutat Res. 1991 Apr;252(2):119-28. doi: 10.1016/0165-1161(91)90012-w.
The genotoxicities of a series of N-nitrosamines were assayed in the wing spot test and a new short-term test of Drosophila melanogaster. In the spot test, larval flies trans-heterozygous for the somatic cell markers mwh and flr3 were fed the test reagents and the wing hairs in adults were inspected for clones expressing the phenotypes of the markers. In the other test, larval stock consisting of meiotic recombination-deficient (Rec-) double mutant mei-9a and mei-41D5 males and repair-proficient Rec+ females were grown on feed containing the reagents and the DNA damages were detected with the preferential killing of the Rec- larvae as an endpoint. The carcinogenic nitrosamines tested, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-butylamine (NDBA), N-nitrosomorpholine (NMOR), N-nitro-sopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR), all showed clearly positive activities in both tests. The activities in the wing spot test were ranked in a sequence of NDMA much greater than NMOR greater than NPIP greater than NDEA greater than NPYR greater than NDBA. A similar ranking was obtained in the repair assay. The genotoxicity of N-nitrosodiphenylamine (NDPhA), carcinogenicity studies of which are inconclusive, was marginal in the spot test. The non-carcinogenic N-nitrosoproline (NPRO) and the non-mutagenic N-nitrosothioproline (NTPRO) were negative in the spot test. NDPhA and NPRO were negative in the repair test as well. The DNA-repair test is thus a convenient technique for estimating the mutagenicity of compounds because of its simplicity compared with the wing spot test. These Drosophila tests may be useful in predicting carcinogenic potentials of compounds.
在果蝇的翅斑试验和一项新的短期试验中，对一系列N - 亚硝胺的遗传毒性进行了测定。在斑点试验中，给体细胞标记mwh和flr3的反式杂合幼虫果蝇喂食受试试剂，然后检查成年果蝇的翅毛，以寻找表达标记表型的克隆。在另一项试验中，由减数分裂重组缺陷（Rec-）的双突变体mei-9a和mei-41D5雄性以及修复 proficient Rec+雌性组成的幼虫群体在含有试剂的饲料上生长，并以Rec-幼虫的优先死亡作为终点来检测DNA损伤。所测试的致癌亚硝胺，N - 亚硝基二甲胺（NDMA）、N - 亚硝基二乙胺（NDEA）、N - 亚硝基二正丁胺（NDBA）、N - 亚硝基吗啉（NMOR）、N - 亚硝基哌啶（NPIP）和N - 亚硝基吡咯烷（NPYR），在两项试验中均显示出明显的阳性活性。在翅斑试验中的活性排序为：NDMA远大于NMOR大于NPIP大于NDEA大于NPYR大于NDBA。在修复试验中也获得了类似的排序。N - 亚硝基二苯胺（NDPhA）的致癌性研究尚无定论，其在斑点试验中的遗传毒性很微弱。非致癌的N - 亚硝基脯氨酸（NPRO）和非诱变的N - 亚硝基硫代脯氨酸（NTPRO）在斑点试验中呈阴性。NDPhA和NPRO在修复试验中也呈阴性。因此，与翅斑试验相比，DNA修复试验因其简单性而成为一种评估化合物诱变性的便捷技术。这些果蝇试验可能有助于预测化合物的致癌潜力。
