Albertini S, Gocke E
Pharma Division, F. Hoffmann-La Roche Ltd; Basel, Switzerland.
Environ Mol Mutagen. 1992;19(2):161-6. doi: 10.1002/em.2850190211.
The liver carcinogen phenobarbital (PB) causes a weak but reproducible increase of the mutant frequency in the Ames test, strain TA1535, without S9. Since there is no obvious chemical basis for a "DNA reactivity" of this compound experiments were performed to obtain information about possible indirect mechanisms of enhancing the number of spontaneous mutant colonies. In the course of the study strong synergistic and comutagenic effects of PB when given in combination with Na-azide or 2-aminoanthracene (2AA) were observed. Not only TA1535 but the complete set of tester strains was responsive. However, PB did not enhance the effects of other mutagens such as 4-nitroquinoline N-oxide or 2-nitrofluorene. It is argued that in strain TA1535 the fixation and expression of spontaneously occurring DNA lesions is amenable to modulation by PB similar to that of Na-azide or 2AA induced lesions. Thus in the usual sense, PB is not genotoxic in the Ames test. Methapyrilene, another liver carcinogen with an assumed nongenotoxic mode of action, showed almost identical properties in these experiments.
肝脏致癌物苯巴比妥（PB）在无S9的情况下，会使Ames试验中TA1535菌株的突变频率出现微弱但可重复的增加。由于该化合物不存在明显的“DNA反应性”化学基础，因此开展了实验以获取有关增加自发突变菌落数量可能的间接机制的信息。在研究过程中，观察到PB与叠氮化钠或2-氨基蒽（2AA）联合使用时具有强烈的协同和共诱变作用。不仅TA1535菌株，整套测试菌株对此都有反应。然而，PB并未增强其他诱变剂（如4-硝基喹啉N-氧化物或2-硝基芴）的作用。有人认为，在TA1535菌株中，自发发生的DNA损伤的固定和表达类似于叠氮化钠或2AA诱导的损伤，易于受到PB的调节。因此，从通常意义上讲，PB在Ames试验中没有基因毒性。另一种假定具有非基因毒性作用模式的肝脏致癌物甲吡咯烷在这些实验中表现出几乎相同的特性。
