Cyclodiene resistance

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). 

Kadous, A.A, Ghiasuddin, S.M., and Matsumura, E. (1983). Differences in the picrotoxinin receptor between cyclodiene-resistant and susceptible strains of the German cockroach. Pesticide Biochemistry and Physiology 19, 157. 

Tanaka K, Matsumura F. Altered picrotoxinin receptor as a cause for cyclodiene resistance in Musca domestica, Aedes aegypti and Blattella germanica. In Clark JM, ed. Membrane Receptor Enzyme Targets Insecicide Action, New York, NY, USA, 1986. New York, NY Plenum, 33-49. 

The first chlordane-related mortality was of three wild birds and was recorded between 1978 and 1981 (Blus et al., 1983). The levels of chlordanes and heptachlor epoxide from the two adult male red-shouldered hawks (Buteo lineatus) and an adult female great horned owl (Bubo virginianus) were within the critical lethal range that has been defined by experimental studies (heptachlor epoxide in brain tissue 3.4-8.3 pg g-1 wet wt. oxychlordane in brain tissue 1.1 5.0 pg g-1 wet wt.). The chlordane poisoning of birds has been reported in several studies in the United States (Blus et al., 1983, 1985 Post, 1951 Stansley Roscoe, 1999). From 1986 to 1990, 122 cases of avian mortality due to chlordane and/or dieldrin were documented in New York, Maryland and New Jersey (Okoniewski Novesky, 1993). High pesticide concentrations were found in cyclodiene-resistant insect populations. These pesticide-tainted insects, when eaten by birds, caused mortalities in the avian populations (Okoniewski Novesky, 1993). 

Table IV. Cyclodiene-Resistance developed in Soil Insects, 1955-65...

The mechanism of cyclodiene-resistance has been very difficult to determine. The hydroxylation of aldrin and dieldrin to aldrin glycol and dieldrin transdiol is a slow process and is not peculiar to resistant strains, while the increased lipoid content... 

Neurotoxic antifeedants from Compositae should provide important leads into strategies that ameliorate the control of the Diabrotica complex. Phytochemicals with combined effects that result in loss of insecticide resistance, reduced feeding, decreased life span, and neurotoxicity in rootworms may be a practical avenue to low chemical input strategies for com production. Also, phytochemical antagonism of cyclodiene resistance may have important consequences to future control of com rootworm by insecticides such as avermectins and pyrethroids (e.g. tefluthrin) which, certainly in the former case (121) and at least secondarily in the latter case (122), act on the GABA gated-chloride ionophore complex. 

Some held stndies have produced evidence snggesting that resistance is developed by wild vertebrates that have been regularly exposed to cyclodienes. Examples... 

The formation of polar metabolites from nonpolar materials may actually facilitate monitoring programs—in many cases the polar chemicals are highly concentrated in certain body fluids such as bile and urine. On the other hand, materials such as certain cyclodienes and polychlorinated biphenyls, which are very lipid soluble and resistant to metabolism, may accumulate and these chemicals may persist in the environment and may be transferred via the food chain to man. There is also interest in these biotransformation processes in lower organisms since the simplicity of these systems may lead to a better understanding of the phylogenetic development of xenobiotic metabolism. 

Resistance to the cyclodienes was evident by this time and was known to extend to lindane and toxaphene but not to DDT. 

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. 

The cyclodiene group of organochlorines was introduced in 1948, starting with chlordane, then aldrin, dieldrin, endrin and toxaphene, and then heptachlor BHC was already available at the close of the war. The experience with housefly control in the Mediterranean countries was that DDT-resistance came in 2 years, and the substitution of BHC was followed by BHC-resistance a year... 

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