Dieldrin resistance

These cross-resistance patterns were studied by J. R. Busvine at the London School of Hygiene. His partly dieldrin resistant strain of M. domestica vicina from the Sudan became 1000-fold resistant when subjected to intense pressure with dieldrin at Slough. 4... 

We now know that a single gene on chromosome IV is responsible for dieldrin resistance in houseflies. The mechanism is still obscure, although recent work has shown that houseflies do metabolise small amounts of dieldrin (28). 

At this time I was interested in the natural tolerance of houseflies to structural analogues of dieldrin and, with Harrison, I soon showed that whereas tolerance to cyclodienes was often related to oxidative detoxication and could be reduced or eliminated by benzodioxole synergists, dieldrin-resistance in houseflies did not respond to synergism and was apparently not a consequence of oxidative detoxication (33) Several laboratories (for their subsequent reviews see 34-36) confirmed the importance of oxidative biotransformations in insects and in 1964-5, at Slough, J. W Ray showed that microsomal preparations from houseflies and other insects contained cytochrome P450 (37) Thus, the links between insect and mammalian biochemical pharmacology were finally and firmly established. 

To test the new formulations, approximately 12 grams of each were placed individually in steel drums containing 35 gallons of water. This was equivalent to about 2 p.p.m. of Abate. Water was withdrawn periodically and analyzed for Abate, and bioassays were conducted simultaneously with third instar Ae. aegypti larvae of the Charlotte Amalie strain (DDT-dieldrin resistant). The tests were conducted for 3 weeks after introducing the toxicant, but during this period no larvae kill was observed in any of the drums. 

A single gene may be responsible for the resistance, and in these cases the level of resistance can be quite high. Well-known examples are the 2000-fold resistance to organophosphates in spider mites, spinosad resistance in western flower thrips, DDT resistance in houseflies, and dieldrin resistance in several Diptera. In other cases, multiple genes are clearly involved in the resistance. Examples are carbaryl resistance in houseflies (Georghiou, 1972), carbaryl resistance in fall army worms (Yu et al., 2003), and malathion resistance in oriental houseflies (Yeoh et al., 1981). 

GABA receptor, a target for several classes of insecticides, consists of two subunits, each with four transmembrane helices as determined from cloning and sequence analysis (641. Expression in Xenopus oocytes requires mRNA from only one of the subunits (651. Dieldrin resistant cockroaches were found to have reduced specific binding of picrotoxinin, which acts on the GABA receptor chloride ion channel (661. 

Mosquito larvae. Three strains of the mosquito Aedes aegypti were used in our qualitative studies the wild type (Rock), Trinidad (DDT resistant), and DLSj (Dieldrin resistant). Many of our early surveys, with these saisitizers as well as with others (17-18, and unpublished results), established that the three strains showed exactly the same response toward the photosaisitized treatmaits. In other words, resistance toward DDT or Dieldrin gave aegypti no resistance toward jtotoactive insecticides. Consequently, the determinations summarized in Table II were made with the Rock strain only. 

Antagonism of the GABA Receptor of Dieldrin-Resistant Houseflies by Fipronil and Its Analogues... 

HJEBOB binding to the head membranes of the dieldrin-resistant (OCR) strain of houseflies was investigated. The OCR houseflies had an alanine-to-serine mutation at the 299-position of the RDL subunit. Scatchard analysis showed that EBOB bound to the head membranes of the OCR houseflies with 4-fold lower affinity than to those of the susceptible (WHO/SRS) strain. The membranes of the OCR strain were found to have 45-fold lower affinity for dieldrin than those of the WHO/SRS strain. By contrast, the membranes of the OCR strain showed only 2-fold lower affinity for fipronil than those of the WHO/SRS strain. The alanine-to-serine mutation does not hinder the binding of fipronil to the housefly GABA receptor. 

We used dieldrin-resistant (OCR) and susceptible (WHO/SRS) strains of houseflies Musca domestica) in the current study. Houseflies possess an RDL... 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

In one example (Lawrence and Casida 1984, Abalis et al. 1985) rat brain microsacs were used to test the action of cyclodiene insecticides such as dieldrin and endrin on the GABA receptors contained therein. The influx of radiolabeled CL into the microsacs via the pore channel of the receptor was inhibited by these chemicals. A similar assay was developed using microsacs from cockroach nerve. Assays with this preparation showed again the inhibitory effect of a cyclodiene (this time heptachlor epoxide) on CL influx. Also, that microsacs from cyclodiene resistant cockroaches were insensitive to the inhibitory effect of picrotoxinin, which binds to the same site on the GABA receptor (Kadous et al. 1983). 

Hayes JR, Hartgrove RW, Hundley SG, et al. 1975. Interaction of endrin and dieldrin with hepatic microsomal cytochrome 450 from the rat, mouse, and endrin-susceptible and resistant pine voles. Toxicol Appl Pharmacol 32 559-565. 

The biotransformation systems involved in insecticide metabolism have been studied in the R and S populations to determine any differences which might be potential contributory factors to or results of insecticide resistance. In addition, the possibility of mixed-function oxidase induction has been investigated. Specifically, the studies have encompassed a seasonal study of microsomal mixed-function oxidase (mfo) components, and studies of aldrin, dieldrin and DDT metabolism. 

Table VIII - Proportion of Dieldrin Formed (percent of total hepatic radioactivity) in Livers of Susceptible (S) and Resistant (R) Fish Exposed to 80 yg/l 14q-aldrin for 6 hra ...

Hepatic mixed-function oxidase activities demonstrated seasonal trends, with higher specific activities in the cold weather months in both populations with few differences in enzyme activities or cytochrome levels between the two populations. Metabolism of aldrin, dieldrin and DDT was similar between the two populations. R fish have larger relative liver size and, therefore, a greater potential for xenobiotic metabolism. However, biotransformation appears to be of minor importance in chlorinated alicyclic insecticide resistance in mosquitofish barriers to penetration appear to be of greater importance and an implied target site insensitivity appears to be the most important factor in resistance. 

In Florida late in 1949 King ( 7) found that oil solutions of dieldrin, parathion, lindane, and toxaphene gave excellent control of resistant strains of larvae and that any of these insecticides would be effective substitutes for DDT. However, some of them are very toxic to animal life and must be used cautiously. 

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