Caenorhabditis elegans mutants resistant to phosphine toxicity show increased longevity and cross-resistance to the synergistic action of oxygen

Cheng, Q., Valmas, N., Reilly, P. E. B., Collins, P. J., Kopittke, R. and Ebert, P. R. (2003) Caenorhabditis elegans mutants resistant to phosphine toxicity show increased longevity and cross-resistance to the synergistic action of oxygen. Toxicological Sciences, 73 1: 60-65. doi:10.1093/toxsci/kfg049


Author Cheng, Q.
Valmas, N.
Reilly, P. E. B.
Collins, P. J.
Kopittke, R.
Ebert, P. R.
Title Caenorhabditis elegans mutants resistant to phosphine toxicity show increased longevity and cross-resistance to the synergistic action of oxygen
Journal name Toxicological Sciences   Check publisher's open access policy
ISSN 1096-6080
Publication date 2003-01-01
Sub-type Article (original research)
DOI 10.1093/toxsci/kfg049
Open Access Status Not Open Access
Volume 73
Issue 1
Start page 60
End page 65
Total pages 6
Place of publication UK
Publisher Oxford University Press
Language eng
Subject C1
270299 Genetics not elsewhere classified
780105 Biological sciences
Abstract 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.
Keyword Toxicology
Methyl Bromide
Oxidative Stress
Oxygen Toxicity
Ros
Mitochondrial Dysfunction
Ems Mutagenesis
Clk-1
Insecticide
Fumigant
Hyperoxia
Stored-product Insects
Rhyzopertha-dominica
Life-span
Strains
Q-Index Code C1
Additional Notes Caenorhabditis elegans mutants resistant to phosphine toxicity show increased longevity and cross-resistance to the synergistic action of oxygen. Toxicological Sciences 73:60-65. (impact factor 3.4) (Identification of novel genes that extend lifespan as well as confer resistance against the fumigant used to protect 80% of the annual grain harvest) (first 2 authors were my PhD students)

 
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