Genetically determined differences in acute responses to diisopropylfluorophosphate

Area of Science:

• Toxicology
• Neuroscience
• Pharmacology

Background:

• Organophosphate compounds, like diisopropylfluorophosphate (DFP), are known neurotoxins.
• Acetylcholinesterase (AChE) inhibition is a primary mechanism of organophosphate toxicity.
• Mouse strain variability can influence responses to toxicological agents.

Purpose of the Study:

• To investigate the acute toxic effects of DFP across different mouse strains (DBA/2Ibg, C57BL/6Ibg, C3H/2Ibg).
• To determine the susceptibility of these strains to DFP-induced intoxication and hypothermia.
• To explore the relationship between AChE activity, body temperature, and DFP dosage in different mouse strains.

Main Methods:

• Administration of DFP via intraperitoneal injection in saline to DBA, C3H, and C57BL mice.
• Measurement of brain acetylcholinesterase (AChE) activity and body temperature at various time points post-injection.
• Determination of LD50 values for DFP in male and female mice of each strain.

Main Results:

• DFP rapidly inhibited brain AChE activity within 5 minutes across all strains.
• C57BL mice exhibited the highest susceptibility to DFP intoxication and hypothermia, with the lowest LD50 values.
• A dose-dependent decrease in body temperature and AChE activity was observed; temperature normalized within 24 hours, except in C57BL mice at high doses.
• A linear relationship was found between maximum temperature depression and residual AChE activity at 24 hours.

Conclusions:

• Significant strain-dependent differences exist in susceptibility to acute DFP toxicity and hypothermia.
• C57BL mice are most vulnerable, while C3H mice are most resistant to DFP effects.
• The observed strain differences in DFP toxicity are not fully explained by differential AChE inhibition alone, suggesting other contributing factors.