Attenuation of radiation toxicity by the phosphine resistance factor dihydrolipoamide dehydrogenase (DLD)

Abstract

Phosphine gas is an excellent fumigant for disinfesting stored grain of insect pests, but heavy reliance on phosphine has led to resistance in grain pests that threatens its efficacy. Phosphine-resistance was previously reported to be mediated by the enzyme DLD. Here we explore the relationship between phosphine toxicity and genotoxic treatments with the goal of understanding how phosphine works. Specifically, we utilized mutant lines either sensitive or resistant to phosphine, gamma irradiation or UV exposure. The phosphine-resistance mutation in the enzyme of energy metabolism, dihydrolipoamide dehydrogenase exhibited cross-resistance to UV and ionizing radiation. Two radiation-sensitive mutants that are defective in DNA repair as well as a mutant that is defective in the activation of the DAF-16 stress response transcription factor all exhibit sensitivity to phosphine that exceeds the sensitivity of the wild type control. A radiation resistance mutation in cep- 1, the p53 orthologue, that is deficient in double strand break repair of DNA and is also deficient in apoptosis causes radiation-resistance results but sensitivity toward phosphine.

Pesticidal Toxicity of Phosphine and Its Interaction with Other Pest Control Treatments

“…Since phosphine has been identified as a redox-active toxin that generates significant oxidative stress [ 5 , 25 ], there is a possible overlap between the biological pathways of the toxic action of the treatments ( Figure 2 ). This event was reported by [ 107 ], where the phosphine-resistant strain of C. elegans showed cross-resistance to UV and gamma radiation. Interestingly, mutations that cause a deficiency in DNA repair, which causes hypersensitivity to radiation also exhibit hypersensitivity to phosphine [ 107 ].…”

“…This event was reported by [ 107 ], where the phosphine-resistant strain of C. elegans showed cross-resistance to UV and gamma radiation. Interestingly, mutations that cause a deficiency in DNA repair, which causes hypersensitivity to radiation also exhibit hypersensitivity to phosphine [ 107 ]. In another study, exposing the nematodes to a mild dose of UV or gamma radiation prior to phosphine fumigation elevated the animals’ tolerance against the fumigant [ 85 ].…”