Genetic variation in paraoxonase activity and sensitivity to diisopropylphosphofluoridate in inbred mice

The mechanism underlying genetic variation in the acute and chronic responses of mice to diisopropylphosphofluoridate (DFP) are unknown. We investigated whether variation in metabolism of organophosphates by A-esterase, as exemplified by the enzyme paraoxonase, was correlated to the degree of sensitivity to DFP in four inbred mouse strains. LD50s and plasma paraoxonase were measured in each strain. We observed genetic variation in both of these measures, but there was no significant correlation between the two measures. We conclude that plasma paraoxonase activity does not underlie genetic variation in sensitivity to the lethal effects of DFP in mice since it does not determine the degree of sensitivity or resistance to DFP.