Resistance to several classes of insecticides was correlated with azinphosmethyl resistance in codling moth, Cydia pomonella (L.), in California. In tests of laboratory and field populations, cross-resistance was positively correlated with azinphosmethyl and two organophosphates (diazinon, phosmet), a carbamate (carbaryl), a chlorinated hydrocarbon (DDT), and two pyrethroids (esfenvalerate and fenpropathrin). Additionally, negatively correlated cross-resistance was identified between azinphosmethyl and two other organophosphates, chlorpyrifos and methyl parathion. Patterns of resistance observed in laboratory colonies were confirmed with field bioassays. In bioassays of field populations, azinphosmethyl resistance was observed to increase from 1991 to 1993, although levels of resistance remained <13-fold. Because orchards with azinphosmethyl resistance have had difficulties with suppression of codling moth, and cross-resistance was found for all tested classes of insecticides, strategies for managing resistance will need to be developed so as to protect current and future control tactics. The two insecticides with negatively correlated cross-resistance are discussed as potential tools for resistance management.

The cytochrome P450-dependent monooxygenases (monooxygenases) are an extremely important metabolic system involved in the catabolism and anabolism of xenobiotics and endogenous compounds. Monooxygenase-mediated metabolism is a common mechanism by which insects become resistant to insecticides as evidenced by the numerous insect species and insecticides affected. This review begins by presenting background information about P450s, the role of monooxygenases in insects, and the different techniques that have been used to isolate individual insect P450s. Next, insecticide resistance is briefly described, and then historical information about monooxygenase-mediated insecticide resistance is reviewed. For any case of monooxygenase-mediated resistance, identification of the P450(s) involved, out of the dozens that are present in an insect, has proven very challenging. Therefore, the next section of the review focuses on the minimal criteria for establishing that a P450 is involved in resistance. This is followed by a comprehensive examination of the literature concerning the individual P450s that have been isolated from insecticide resistant strains. In each case, the history of the strain and the evidence for monooxygenase-mediated resistance are reviewed. The isolation and characterization of the P450(s) from the strain are then described, and the evidence of whether or not the isolated P450(s) is involved in resistance is summarized. The remainder of the review summarizes our current knowledge of the molecular basis of monooxygenase-mediated resistance and the implications for the future. The importance of these studies for development of effective insecticide resistance management strategies is discussed.

Insecticide resistance has been a problem in all insect groups that serve as vectors of emerging diseases. Although mechanisms by which insecticides become less effective are similar across all vector taxa, each resistance problem is potentially unique and may involve a complex pattern of resistance foci. The main defense against resistance is close surveillance of the susceptibility of vector populations. We describe the mechanisms of insecticide resistance, as well as specific instances of resistance emergence worldwide, and discuss prospects for resistance management and priorities for detection and surveillance.

Tobacco budworm,Heliothis virescens,larvae were collected from wild velvet leaf in Macon Ridge (LA) where insecticide resistance in cotton was previously reported. The initial resistance levels were 58.0-fold for thiodicarb and 16.0-fold for cypermethrin compared to a susceptible laboratory population. Selection of this Macon Ridge population with thiodicarb on cotton increased resistance for thiodicarb to 172.9-fold and resulted in cross-resistance for cypermethrin to 161.3-fold compared to the susceptible control. Thiodicarb-selected Macon Ridge budworms were also resistant to methyl parathion (7.6-fold), profenofos (59.9-fold), and azinphosmethyl (>38.8-fold). Cytochrome P450 metabolism ofp-nitroanisole was elevated 30.1-, 16.8-, and 18.8-fold in midgut, fat body, and carcass, respectively, of the selected Macon Ridge budworms. The P450 content was also increased. Ester hydrolysis of 1-naphthyl acetate andp-nitrophenyl acetate as well as 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene glutathioneS-transferase activity were elevated approximately 2-fold with some variability among the specific tissues examined. Piperonyl butoxide increased thiodicarb toxicity by 14.8-fold, methyl parathion by 9.3-fold, and cypermethrin by 19.4-fold.S,S,S-Tributylphosphorothioate increased thiodicarb toxicity by 14.5-fold, methyl parathion by 6.6-fold, and profenofos by 7.2-fold. These results suggests that both cytochrome P450 and esterase play an important role in tobacco budworm resistance and cross-resistance between carbamates, organophosphates, and pyrethroids. Acetylthiocholine hydrolysis was 3.4- and 3.5-fold insensitive to paraoxon and methomyl, respectively, in the thiodicarb-selected Macon Ridge strain. Microassays based onp-nitroanisole andp-nitrophenyl acetate metabolism were successfully used to diagnose resistance in field populations of the tobacco budworm in different geographical areas of the U.S.

Vertebrates and invertebrates both have GABA (γ-aminobutyric acid) as a major inhibitory neurotransmitter1,2. GABAA receptors in vertebrates assemble as heteromultimers to form an integral chloride ion channel3. These receptors are targets for drugs and pesticides4 and are also implicated in seizure-related diseases5,6. Picrotoxinin (PTX) and cyclodiene insecticides are GABAA receptor antagonists which competitively displace each other from the same binding site7. Insects8 and vertebrates9 showing resistance to cyclodienes also show cross-resistance to PTX. Previously, we used a field-isolated Drosophila mutant Rdl (Resistant to dieldrin)10 insensitive to PTX and cyclodienes to clone a putative GABA receptor11. Here we report the functional expression and novel pharmacology of this GABA receptor and examine the functionality of a resistance-associated point mutation (alanine to serine) within the second membrane-spanning domain, the region thought to line the chloride ion channel pore. This substitution is found globally in Drosophila populations12. This mutation not only identifies a single amino acid conferring high levels of resist-ance to the important GABA receptor antagonist PTX but also, by conferring resistance to cyclodienes, may account for over 60% of reported cases of insecticide resistance13.