Cheng Qiang, Valmas Nicholas, Reilly Paul E B, Collins Patrick J, Kopittke Rosemary, Ebert Paul R
Department of Biochemistry and Molecular Biology, The University of Queensland, St. Lucia, Australia.
Toxicol Sci. 2003 May;73(1):60-5. doi: 10.1093/toxsci/kfg049. Epub 2003 Apr 15.
Phosphine (hydrogen phosphide, PH3) is the fumigant most widely used to protect stored products from pest infestation. Despite the importance of this chemical, little is known about its mode of action. We have created three phosphine-resistant lines (pre-1, pre-7, pre-33) in the model organism C. elegans, with LC50 values 2, 5, and 9 times greater than the fully susceptible parental strain. Molecular oxygen was shown to be an extremely effective synergist with phosphine as, under hyperoxic conditions, 100% mortality was observed in wild-type nematodes exposed to 0.1 mg/l phosphine, a nonlethal concentration in air. All three mutants were resistant to the synergistic effects of oxygen in proportion to their resistance to phosphine with one mutant, pre-33, showing complete resistance to this synergism. We take the proportionality of cross-resistance between phosphine and the synergistic effect of oxygen to imply that all three mutants circumvent a mechanism of phosphine toxicity that is directly coupled to oxygen metabolism. Compared with the wild-type strain, all three mutants have an extended average life expectancy of from 12.5 to 25.3%. This is consistent with the proposed involvement of oxidative stress in both phosphine toxicity and ageing. Because the wild-type and mutant nematodes develop at the same rate, the longevity is unlikely to be caused by a clk-type reduction in oxidative metabolism, a potential alternative mechanism of phosphine resistance.
磷化氢(膦,PH₃)是用于保护储存产品免受害虫侵扰的使用最为广泛的熏蒸剂。尽管这种化学品很重要,但其作用方式却鲜为人知。我们在模式生物秀丽隐杆线虫中创建了三个抗磷化氢品系(pre - 1、pre - 7、pre - 33),其半数致死浓度(LC50)值分别比完全敏感的亲本菌株高2倍、5倍和9倍。分子氧被证明是磷化氢的一种极其有效的增效剂,因为在高氧条件下,暴露于0.1毫克/升磷化氢(在空气中为非致死浓度)的野生型线虫出现了100%的死亡率。所有三个突变体对氧的增效作用的抗性与它们对磷化氢的抗性成比例,其中一个突变体pre - 33对这种增效作用表现出完全抗性。我们认为磷化氢与氧的增效作用之间的交叉抗性成比例意味着所有这三个突变体规避了一种与氧代谢直接相关的磷化氢毒性机制。与野生型菌株相比,所有三个突变体的平均预期寿命延长了12.5%至25.3%。这与氧化应激参与磷化氢毒性和衰老的观点一致。由于野生型和突变型线虫的发育速度相同,寿命延长不太可能是由clk型氧化代谢降低引起的,而氧化代谢降低是磷化氢抗性的一种潜在替代机制。