Graf U, van Schaik N
Institute of Toxicology, Swiss Federal Institute of Technology.
Mutat Res. 1992 Feb;271(1):59-67. doi: 10.1016/0165-1161(92)90032-h.
The two tester strains of the high bioactivation (HB) cross for the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster developed by Frölich and Würgler possess high metabolic capacity to activate promutagens. These strains contain chromosomes 1 and 2 of the DDT-resistant stock Oregon R(R) which exhibits a high constitutive level of cytochrome P450. However, they show several disadvantages for routine application, such as disturbed wing hair patterns in certain areas of the wing, making spot classification difficult, and a delay in development of the larvae. We have established and evaluated an improved HB cross (ORR; flr3 females and mwh males) producing ORR heterozygous individuals. These develop normally and have a normal, undisturbed wing hair pattern while exhibiting high bioactivation. The hybrid larvae of the improved HB cross show P450-dependent bioactivation capacity equal to or even slightly higher than those of the original HB cross. This was demonstrated by measuring the genotoxic activity of the promutagens diethylnitrosamine, 7,12-dimethylbenz[a]anthracene, N-nitrosopyrrolidine, and urethane. In addition, the improved HB cross has a sensitivity to the direct-acting alkylating agent ethyl nitrosourea equal to that of the standard cross. The main advantage of the improved HB cross is to combine the high bioactivation capacity with the ease of scoring the wings using the same criteria as for the standard cross.
弗罗利希和维尔格勒开发的用于果蝇翅体细胞突变和重组试验(SMART)的高生物活化(HB)杂交的两种测试菌株具有高代谢能力来激活前诱变剂。这些菌株含有抗滴滴涕品系俄勒冈R(R)的1号和2号染色体,该品系表现出高水平的细胞色素P450组成型表达。然而,它们在常规应用中存在几个缺点,例如翅的某些区域翅毛模式紊乱,使得斑点分类困难,以及幼虫发育延迟。我们建立并评估了一种改良的HB杂交(ORR;flr3雌性和mwh雄性),产生ORR杂合个体。这些个体发育正常,具有正常、未受干扰的翅毛模式,同时表现出高生物活化能力。改良的HB杂交的杂种幼虫表现出的依赖细胞色素P450的生物活化能力等于或甚至略高于原始HB杂交的幼虫。这通过测量前诱变剂二乙基亚硝胺、7,12 - 二甲基苯并[a]蒽、N - 亚硝基吡咯烷和尿烷的遗传毒性活性得到了证明。此外,改良的HB杂交对直接作用的烷基化剂乙基亚硝基脲的敏感性与标准杂交相同。改良的HB杂交的主要优点是将高生物活化能力与使用与标准杂交相同的标准对翅进行评分的简便性结合起来。