Pesticide Resistance Strategies and Tactics for Management (1986) / Chapter Skim
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Resistance to 4-Hydroxycoumarin Anticoagulants in Rodents
Resistance to 4-Hydroxycoumarin Anticoagulants in Rodents
Pages 87-99
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From page 87... ...
The most widespread and well-documented example is resistance to warfarin in rodents. It has been demonstrated in Rattus norvegicus and Mus musculus that inheritance of warfarin resistance is monogenic and the gene is closely linked to that for coat color.
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From page 88... ...
Resistance to coumarin anticoagulants in rodents is the most widespread and thoroughly investigated example of inheritable pesticide resistance in vertebrates and will be discussed in detail. A laboratory mouse strain has been developed that showed a 1.7-fold tolerance to DDT when compared to the original susceptible strain (Ozburn and Morrison, 19621.
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From page 89... ...
was isolated from moldy sweet clover hay in 1939 (Link, 19441. Following observations that cattle that were fed on spoiled sweet clover hay developed a fatal haemorrhagic malady, dicoumarol was subsequently clinically used as a prophylactic agent against thrombosis.
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From page 90... ...
Analysis of blood-clotting time 24 hours after treatment showed that rats that were either homozygous or heterozygous for the Welsh warfarin resistance gene had normal prothrombin levels, but homozygous-susceptible animals had elongated clotting times. The implication was that warfarinresistant animals were able to utilize vitamin K 2,3-epoxide in the presence
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From page 91... ...
norvegicus until recently have only been carried out using animals derived from wild Welsh rats (Pool et al., 1968; Greaves and Ayres, 19691. These rat strains undoubtedly have an altered hepatic microsomal vitamin K epoxide reductase with reduced sensitivity to warfarin.
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From page 92... ...
Highly purified rat-liver cytosolic DT-diaphorase reduced vitamin Kit (Fasco and Principe, 1982~; this reduction was dicoumarol- but not warfarin-sensitive. The results are inconsistent with the warfarin-sensitive NADH or DDTdependent vitamin K~ hydroquinone formation observed with crude rat-liver microsomal fractions.
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From page 93... ...
The increased toxicity is assigned to the highly lipophilic nature of the substituents at the 3-position of the 4-hydroxycoumarin nucleus (Hadler and Shadbolt, 1975; Dubock and Kaukeinen, 1978~. Initial laboratory studies and field trials indicated that these compounds could effectively control warfarin-resistant rat and mouse populations (Hadler, 1975; Hadler et al., 1975; Hadler and Shadbolt, 1975; Redfern et al., 1976; Rennison and Dubock, 1978; Redfern and Gill, 1980; Lund, 1981; Richards, 1981; Rowe et al., 19811.
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From page 94... ...
norvegicus was developed a few years after this compound was introduced as a rodenticide (Redfern and Gill, 19781. A significant widespread incidence of difenacoum resistance was detected in rat populations across an area of English farmland (Greaves et al., 1982a)
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From page 95... ...
Almost all such studies used rat strains derived from wild Welsh rats, and comparative studies have not always used a suitable susceptible control. At least one hypothesis of the mechanism of resistance was erroneously based on a strain difference.
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From page 96... ...
1983. Formation of hydroxyvitamin K by vitamin K epoxide reductase of warfarin resistant rats.
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From page 97... ...
1984. Solubilization and characterization of vitamin K epoxide reductase from normal and warfarin-resistant rat liver microsomes.
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From page 98... ...
1979. Warfarin resistance genotype determination in the Norway rat Rattus norvegicus.
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From page 99... ...
1967. Die Auswahl von Rodentiziden fur die Rattenvertilgungen und fur die Beibehaltung eines rattenfreien Zustandes.
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