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Pesticide Resistance: Strategies and Tactics for Management.
1986. National Academy Press, Washington, D.C.
Genetics and Biochemistry of
Insecticide Resistance in Arthropods
Prospects for the Future
.
FREDERICK W. PLAPP, JR.
Insecticide resistance in the housefly has a fairly simple genetic
basis. There is one gene for decreased uptake of insecticides, one
gene for target-site resistance to each insecticide type, and one major
gene for metabolic resistance to all insecticides. The last interacts
with minor genes located elsewhere in the genome. Based on limited
data, resistance patterns are similar in other species.
Evidence is presented that target-site resistance to pyrethroidsl
DDT and to cyclodienes is controlled by changes in regulatory genes
determining the number of receptor protein molecules synthesized.
Resistance in both is recessive to susceptibility.
The product of the major gene for metabolic resistance appears
to be a receptor protein that recognizes and binds insecticides and
then induces synthesis of appropriate detoxifying enzymes. Different
types of enzymes, for example, oxidases, esterases, and glutathione
transferases, are coordinately induced. The effect of the gene is
qualitative, that is, it determines the specific form of detoxifying
enzyme synthesized. Inheritance is codominant.
Possible solutions to resistance include using synergists such as
chlordimeform, which appear to act by increasing the binding of
pyrethroid insecticides to their target-site proteins; using agonists,
which successfully compete with insecticides for recognition by the
receptor protein; and using either mixtures of insecticides or insec-
ticides composed of multiple isomers.
INTRODUCTION
Resistance to insecticides in arthropods is widespread (Georghiou and
Mellon, 1983), with at least 400 species resistant to one or more insecticides.
74
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INSECTICIDE RESISTANCE IN ARTHROPODS
75
In some species, populations are resistant to nearly every insecticide ever
used to control them and, often, to related chemicals to which the population
has never been exposed. Resistance, at least in the house fly, has a fairly
simple and straightforward genetic basis. Extensive genetic studies in other
species, most notably Lucilia cuprina and Drosophila melanogaster, have
indicated a similar situation. The biochemistry of resistance is also compre-
hensible, particularly when there is an adequate understanding of the genetics
of resistant populations.
GENETIC MECHANISMS CONFERRING RESISTANCE
A very important question is, How many genes for resistance are there?
Are there multiple genes for resistance, each conferring resistance to a narrow
range of insecticides, or are there only a few genes, each conferring resistance
to a wide array of insecticides? If there are numerous genes then cross-
resistance associated with each gene should be limited, and new insecticides
would solve the problem. Conversely, if a limited number of genetic mech-
anisms is involved, then resistant populations should show resistance to
insecticides to which they have never been exposed. The second hypothesis
is more frequently true. Thus, developing new insecticides that are closely
related to existing insecticides in either mode of action or pathways of me-
tabolism will not solve the problem.
If only a few major genes confer resistance to insecticides, it should be
possible to characterize the mechanisms controlled by each gene. Once this
is done, it may be possible to devise solutions and regain our ability to deal
with populations recalcitrant to chemical control.
Standard neo-Darwinian models (Moore, 1984) suggest that change occurs
as a result of accumulation of multiple mutations, each mutation contributing
a minute amount to the total; that is, insecticide resistance should be poly-
genic, but it is not (Whitten and McKenzie, 1982~. In field populations
resistance is almost invariably due to a single major gene. Therefore, standard
evolutionary theory does not seem to apply to the development of resistance.
A regulatory gene hypothesis is a more likely model to account for change,
particularly at the population or subspecific level. Such genes, which control
time and nature of expression of structural genes, are more likely to provide
the genetic basis of adaptive variation such as the development of resistance
(Levin, 19841. In my opinion, available data on resistance offer considerable
support for Levin's hypothesis. In this paper I shall summarize both genetic
and biochemical evidence that changes in regulatory genes are of major
importance in insecticide resistance.
Two types of regulatory genes seem to be present, and both differ in
inheritance and biochemistry. One type exhibits all-or-none inheritance (fully
dominant or recessive) and appears to involve changes in the amount of
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76
MECHANISMS OF RESISTANCE TO PESTICIDES
protein synthesized. The second shows codominant (intermediate) inheritance
and involves changes in the nature of proteins synthesized.
Quantitative resistance (that type involving differences in amount of proteins
synthesized) is similar in nature to certain bacterial operons. Resistance of this
type apparently involves regulatory elements located adjacent to the structural
genes in question. Change does not occur in the structural gene, but in an
adjacent, distinct, genetic element. If it were in the structural gene, inheritance
would be additive. Since it is not, the evidence is that a separate protein (i.e.,
the product of a distinct gene) must be the site of variation. Regulators of this
type have been defined as "near" regulators (Paigen, 19791.
The second type, qualitative resistance, appears to represent a mechanism
allowing for production of altered forms of particular detoxifying enzymes
in resistant as compared to susceptible insects. Genetic studies with the house
fly (Plapp, 1984) show that change at a single genetic locus appears to control
resistance associated with multiple detoxification enzymes. A similar mech-
anism can be inferred from earlier studies with D. melanogaster (Kikkawa,
1964a,b). Since one locus appears to act on a variety of enzymes, the gene
probably is not adjacent to the enzymes whose activity it regulates. Such
regulators have been defined as "distant" regulators (Paigen, 1979), and
such systems can be considered "regulons" (Plapp, 19841. According to
Paigen, these systems are characterized by their codominant inheritance rather
than the all-or-none type of similar bacterial systems.
GENETICS OF RESISTANCE
The number of major genes conferring resistance to insecticides in the
house fly (and presumably other species) is limited. The list of known re-
sistance genes includes:
· pen for decreased uptake of insecticides. This chromosome III gene
is inherited as a simple recessive. By itself, pen confers little resistance to
any insecticide, seldom more than two- to three-fold. It appears to be more
important as a modifier of other resistance genes. In such cases pen may
double resistance levels, for example, from 50- to 100-fold.
· kdr- for knockdown resistance to DDT and pyrethroids. This gene is
a chromosome III recessive at a locus distinct from pen. It confers resistance
to DOT and all analogs and to pyrethrins and all synthetic analogs. Low-
level (kdr) and high-level (super kdr) alleles have been reported. The gene
probably involves modifications at the target site of the insecticides.
· dld-r for resistance to dieldrin and all other cyclodienes. This is a
chromosome IV gene whose inheritance is incompletely recessive. Resistance
appears to involve change at the target site of these insecticides.
· AChE-R for altered acetylcholinesterase, the target site for organo
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INSECTICIDE RESISTANCE IN ARTHROPODS
77
phosphate (OP) and carbamate insecticides. The gene is located on chro-
mosome II and is inherited as a codominant. Different alleles appear to confer
different levels of resistance to multiple organophosphate and carbamate
insecticides (Oppenoorth, 19821.
The house fly's metabolic resistance to many types of insecticides, in-
cluding OPs, carbamates, pyrethroids, DDT, and juvenile hormone analogs,
is associated with a gene or genes on chromosome II. This type of resistance
was long thought to be due primarily to mutations in structural genes for the
specific enzymes. Earlier work had shown that resistance genes were located
at a variety of loci on chromosome II (Hiroyoshi, 1977; Tsukamoto, 19831.
More recent work (Wang and Plapp, 1980; Plapp and Wang, 1983) suggests
that inversions or other rearrangements of the chromosome are present in
many resistant strains and are of sufficient extent to explain the apparent
differences in gene location on the chromosome, that is, only one gene seems
to be present, but it is not always located at the same place relative to other
genes on chromosome II Based on these results the idea of multiple structural
genes for metabolic resistance on chromosome II becomes more tenuous,
and the idea of a common resistance gene becomes more logical.
Close linkage (and, therefore, possible allelism) exists among genes for
metabolic resistance to insecticides in other insect species as well. Examples
include the gene RI (for resistance to insecticides) located at 64.5-66 on
chromosome II of Drosophila melanogaster, a locus conferring resistance to
organophosphates, carbamates, and DDT (Kikkawa, 1964a,b), and major
genes for metabolic resistance to diazinon and malathion in numerous pop-
ulations of Lucilia cuprina (Hughes et al., 19841. Other evidence for allelism
has been reported for malathion resistance in different populations of Tri-
bolium castaneum (R. W. Beeman, U.S. Department of Agriculture, Man-
hattan, Kansas, personal communication, 1983~. In fact, our knowledge of
the genetics of resistance in insects other than dipterans is so inadequate that
we can only guess as to the precise nature of the genetic mechanisms involved.
Research has shown that resistance to different classes of insecticides is
associated with a particular linkage group, but the number of genes involved
is unknown. Genetically, the most feasible approach to this problem is to
perform allelism tests. This method has demonstrated allelism of genes for
reduced uptake of insecticides (pen) in American and European house fly
populations (Sawicki, 1970) and for organophosphate resistance in spider
mites (Ballantyne and Harrison, 19671. I have recently been doing such tests
on several house fly strains with metabolic resistance to various organo-
phosphates associated with chromosome II and with chromosome II resistance
to DDT and organophosphates within a strain. All data indicate allelism of
the genes.
Although chromosome II has been shown to make a major contribution
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MECHANISMS OF RESISTANCE TO PESTICIDES
to metabolic resistance in the house fly, minor genes on other chromosomes
make additional contributions. An assay of total levels of resistance is made
by crossing resistant strains with susceptible strains containing mutant mark-
ers on multiple chromosomes. Recent work in my laboratory has shown that
the contribution to metabolic resistance of chromosomes other than II is not
expressed in the absence of chromosome II and is inherited as incomplete
recessives. Such resistance is similar in inheritance to that described previ-
ously for pen, kdr, and dId-r.
Position also affects the expression of resistance associated with chro-
mosome II. Strains showing a major (20 to 30 percent) reduction in recom-
bination values between the resistance gene and the mutation carnation eye
(car) have increased levels of resistance, compared with strains showing
smaller reductions in recombination values (Plapp and Wang, 19831. Thus,
the location of the gene on chromosome II is important in determining the
level of resistance present.
In summary four types of resistance, pen, kdr, dld-r, and metabolic,
associated with chromosomes other than II, are inherited as incompletely or
fully recessive characters. In contrast, altered acetycholinesterase resistance
and metabolic resistance on chromosome II are inherited as codominants.
The level of resistance associated with the major chromosome II gene for
metabolic resistance varies with the location of the gene on the chromosome.
BIOCHEMISTRY OF RESISTANCE
This area has been intensively studied for the last 30 years. Earlier work
concentrated on mechanisms associated with metabolic resistance and iden-
tified a number of enzyme systems concerned with resistance (Tsukamoto,
1969; Oppenoorth, 1984~. Recent studies have dealt with mechanisms in-
volved in nonmetabolic (target site) resistance. The availability of genetic
stocks purified to contain individual mechanisms proved invaluable to these
studies.
High-affinity receptors for DDT and pyrethroids are present in insects
(Chang and Plapp, 1983a,c). House flies possessing the gene kdr for target-
site resistance bound less insecticide than susceptible flies. Resistant flies
had fewer target-site receptors than susceptible flies (Chang and Plapp, 1983b).
Further, binding affinity between preparations from R and S strains did not
differ. Therefore, the major difference between strains was strictly quanti-
tative, that is, in receptor numbers, and not qualitative, that is, in receptor
affinity.
Similar studies on cyclodiene mode of action/mechanism of resistance
have been reported by Matsumura and coworkers. Kadous et al. (1983)
reported that cyclodiene-resistant cockroaches were cross-resistant to the
plant-derived neurotoxicant picrotoxinin and, further, that nerve components
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INSECTICIDE RESISTANCE IN ARTHROPODS
79
from resistant cockroaches bound significantly less [3H] a-dihydropicrotox-
inin than similar preparations from susceptible insects. The receptor was
sensitive to all cyclodiene insecticides (Tanaka et al., 19841. Similar studies
with susceptible and cyclodiene-resistant house flies have shown reduced
binding in resistant insects (K. Tanaka and F. Matsumura, Michigan State
University, East Lansing, Michigan, personal communication, 1984), sug-
gesting that the number of receptor binding sites is decreasing.
Thus, quantitative decreases in numbers of target sites may be involved
in target-site resistance to both DDT/pyrethroids and cyclodienes. At first
glance it may appear contradictory for resistant insects to have fewer target-
sites than susceptible insects. Decreased receptor numbers probably confer
resistance by a needle-in-the-haystack approach (Lund and Narahashi, 1981a,b);
the decrease in number may make it less likely for a toxicant to reach target-
sites.
Decreases in target-site numbers are consistent with the genetics of resis-
tance to these insecticides. If the change were in the target-sites themselves,
inheritance would be additive; R/S heterozygotes would be intermediate be-
tween the parents in resistance. Inheritance being all-or-none agrees with the
idea of quantitative change. The specific mutations conferring resistance are
probably in genes coding for proteins that determine the number of target-
site proteins synthesized. Here, heterozygotes would have the normal number
of receptors since the diffusible protein product of the wild-type regulatory
gene would act on both structural genes. Only the resistant homozygotes,
those with two mutant genes, would produce fewer target-site receptor pro-
teins than normal. This activity is an example of bans dominance; the protein
product of a regulatory gene influences the expression of a specific structural
gene on both members of a chromosome pair.
The precise biochemical mechanism of the major gene for metabolic re-
sistance to insecticides is not yet known with certainty, although a single
gene locus is probably involved. Since all structural genes coding for de-
toxification enzymes are probably not at the same site, a common controlling
mechanism might be responsible.
The key to metabolic resistance is induction. Induction of different de-
toxifying enzymes is coordinate (Plapp, 1984~; that is, exposure to chemicals
that induce one detoxifying enzyme induces several. Mixed-function oxi-
dases, glutathione transferases, and DDT dehydrochlorinase are coordinately
induced in the house fly (Plapp, 1984), as are oxidases and glutathione
transferases in Spodoptera (Yu, 19841. When the products of several struc-
tural genes (enzymes) respond to the same stimulus, they must be responding
to the protein product of a separate gene, a genetic element that is distinct
from the elements that define the enzymes themselves.
The finding is not original. It comes from the research of Monod and
Jacob on induction in E. coli. As reviewed by Judson the critical idea in
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80
MECHANISMS OF RESISTANCE TO PESTICIDES
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Representative terms from entire chapter:
house fly
INSECTICIDE RESISTANCE IN ARTHROPODS
Insecticides
oPs
Carban,~1es - \
Pyrethroids
DOT
JHAs
Others
~\
Detoxifying Enzymes
Resistance Gene MFOs
/~
Single Gene, |_
Chromosome ~
Bomb Gene Product, a /~'0<,
82
MECHANISMS OF RESISTANCE TO PESTICIDES
are designed to counter. Target-site synergism may exist, however, and in
at least one case the use of such a synergist has blocked the development of
resistance.
Several years ago we reported that the miticide-ovicide chlordimeform was
found to be strongly synergistic with several hard-to-metabolize insecticides,
including toxaphene and DDT, to which resistance was present in the tobacco
budworm (Plapp, 1976; Plapp et al., 19761. Since then chIordimeform syn-
ergism has been reported in the new, metabolically stable synthetic pyreth-
roids (Plapp, 1979; Rajakulendren and Plapp, 19821. Many formamidines
are synergistic with pyrethroids and other insecticides against several ar-
thropod species (El-Sayed and Knowles, 1984a,b). The mechanism for this
synergism may be that chlordimeform is acting as a target-site synergist
(Chang and Plapp, 1983c).
Chlordimeform may block pyrethroid resistance in Heliothis (Crowder, et
al., 19841. Selection of H. virescens with permethrin resulted in 37-fold
resistance within a few generations. Parallel selection with permethrin-chlor-
dimeform combinations prevented resistance development.
Therefore, limited data are available suggesting that chlordimeform may
synergize insecticides against insects in cases of target-site resistance and
block development of such resistance. Since the new synthetic pyrethroids
will probably be subject to kdr-type resistance, the use of such combinations
offers a possible way to manage the problem.
Metabolic resistance has been attacked by a variety of approaches, pri-
marily the use of synergists designed to poison the enzymes involved in
detoxification. Since the work described in this paper indicates that a single
gene is of primary importance in this resistance, different approaches may
be possible. Rather than poisoning the detoxifying enzymes, it may be pos-
sible to affect the receptor protein by using agonists that compete with in-
secticides for recognition sites on xenobiotic receptor proteins.
This idea may already have been demonstrated. Ranasinghe and Georghiou
(1979) selected an organophosphate-resistant mosquito population with three
regimens. These were temephos only, temephos plus the antioxidant synergist
piperonyl butoxide, and temephos plus DEF. DEF, S,S,S-tributyl phospho-
rotrithioate, is a plant defoliant that inhibits oxidases and esterases. I suggest
that it is a receptor agonist. Selection with temephos resulted in the rapid
development of a high level of resistance. The same thing occurred, but
slightly slower, with temephos plus piperonyl butoxide. Selection with te-
mephos plus DEF quickly restored a near-normal level of susceptibility to
the test population.
The authors were unable to offer an explanation for the results of the
temephos/DEF selection. I believe that DEF has a high affinity for the receptor
protein, which recognizes temephos as a xenobiotic. With the temephos/DEF
selection the receptor protein increased its ability to recognize and bind DEF
INSECTICIDE RESISTANCE IN ARTHROPODS
83
and simultaneously lost its ability to recognize, bind, and, thus, respond to
temephos.
Other work with DEF as a synergist has been done with Lucilia (Hughes,
19821. Preexposure to DEF significantly synergized diazinon, while simul-
taneous exposure to DEF and diazinon was much less effective. Again the
results agree with a receptor-level effect for DEF.
Another approach to overcoming metabolic resistance involves using in-
secticides composed of two isomers. The major example of this effect in-
volves phenylphosphonates of the EPN series. These insecticides have four
different substituents attached to the central phosphorus atom. They exist as
plus and minus isomers. Insects with metabolic resistance to the more typical
dialkyl phenyl phosphorothioates show little or no cross-resistance to the
phenylphosphonates. The single gene hypothesis for metabolic resistance
offers an explanation. If only one receptor gene is of primary importance in
metabolic resistance, its protein product can recognize either the plus or the
minus isomer, but not both at once. If this is so, then synthesis of enzymes
of high specific activity toward only one isomer will be induced. An example
of the use of two isomer organophosphates to circumvent resistance involves
profenofos to control multiresistant populations of Spodoptera littoralis in
Egypt (Dittrich et al., 19791. I have confirmed these findings of lack of
resistance to the two isomer OPs in fly strains with metabolic resistance to
single isomer OPs. It may be a general phenomenon. This idea may not be
practical, however, because of the delayed neurotoxicity syndrome associated
with at least some of these organophosphates (Metcalf and Metcalf, 19841.
A final approach involves using multiple isomers of an insecticide. The
idea is that the two will compete for the receptor protein just as the plus and
minus isomers of the phenylphosphonates compete. I tested this idea by
comparing the toxicity of dimethyl and diisopropyl isomers of parathion,
alone and in combination, to susceptible and resistant house flies. Toxicities
of the mixture were additive to susceptible flies, but synergistic with resistant
flies. These results suggest that using mixed alkyl isomers of dialkyl phen-
ylphosphates and phosphorothioates might prove quite effective for over-
coming resistance. Again the mechanism responsible may be the lack of
ability of a single resistance gene to handle multiple chemicals simulta-
neously.
CONCLUSION
Resistance genetics in the house fly is comparatively simple. The studies
described here would not have been possible without the availability of mutant
stocks to identify different chromosomes and to map resistance gene locations
on specific chromosomes. Such studies are currently not feasible with most
resistant species, due to lack of mutant markers. Nevertheless, what is true
84
MECHANISMS OF RESISTANCE TO PESTICIDES
for house flies and other higher Diptera in the way of resistance genetics is
probably true for other insects; that is, the genetic mechanisms involved are
probably ubiquitous rather than specific.
Based on the genetics, it is possible to develop a comprehensive theory
of resistance. Resistance is best understood as being due to changes in reg-
ulatory genes controlling the amount or nature of target proteins or enzymes
synthesized. From this understanding, approaches to solving the problem
become feasible, at least for metabolic resistance. Solutions involve using
mixtures of insecticides or using insecticides composed of several isomers.
The mixture approach will work because change at only a single locus is
involved. Not all components of an insecticide need to be toxic; some may
work primarily as receptor agonists rather than enzyme inhibitors.
Nothing in the foregoing should be interpreted, however, as an opinion
that resistance is subject to perfect and/or complete suppression via chemical
means. I have no doubt that, in the long term, life will always overcome
chemistry and find ways to persevere. The best that can be said is that if we
are lucky, we should be able to suppress resistance to such an extent that
we can live with it.
REFERENCES
Ballantyne, G. H., and R. A. Harrison. 1967. Genetic and biochemical comparisons of organo-
phosphate resistance between strains of spider mites (Tetranychus species). Entomol. Exp. Appl.
10:231-239.
Britten, R. J., and E. H. Davidson. 1969. Gene regulation for higher cells: A theory. Science
169:349-357.
Chang, C. P., and F. W. Plapp, Jr. 1983a. DDT and pyrethroids: Receptor binding and mode of
action in the house fly. Pestic. Biochem. Physiol. 20:76-85.
Chang, C. P., and F. W. Plapp, Jr. 1983b. DDT and pyrethroids: Receptor binding and mechanism
of knockdown resistance (kdr) in the house fly. Pestic. Biochem. Physiol. 20:86-91.
Chang, C. P., and F. W. Plapp, Jr. 1983c. DDT and synthetic pyrethroids: Mode of action,
selectivity, and mechanism of synergism in the tobacco budworm, Heliothis virescens (F.), and
a predator Chrysopa carnea Stephens. J. Econ. Entomol. 76:1206-1210.
Crowder, L. A., M. P. Jensen, and T. F. Watson. 1984. Permethrin resistance in the tobacco
budworm, Heliothis virescens. Pp. 223-224 in Proc. Beltwide Cotton Conf., Atlanta, Gal, January
9-12, 1984.
Dittrich, V., N. Luetkemeier, and G. Voss. 1979. Monocrotophos and profenofos: Two organo-
phosphates with a different mechanism of action in resistant races of the Egyptian cotton leafworm
Spodoptera littoralis. J. Econ. Entomol. 72:380-384.
El-Sayed, G. N., and C. O. Knowles. 1984a. Formamidine synergism of pyrethroid toxicity to two-
spotted spider mites (Acari: Tetranychidae). J. Econ. Entomol. 77:23-30.
El-Sayed, G. N., and C. O. Knowles. 1984b. Synergism of insecticide activity to Heliothis zea
(Boddie) by formanilides and formamidines. J. Econ. Entomol. 77:872-875.
Georghiou, G. P., and R. B. Mellon. 1983. Pesticide resistance in time and space. Pp. 1-46 in
Pest Resistance to Pesticides, G. P. Georghiou and T. Saito, eds. New York: Plenum.
Hallstrom, I. P. 1984. Cytochrome P4so in Drosophila melanogaster: Activity, Genetic Variation
and Regulation. Ph.D. dissertation. University of Stockholm, Sweden.
INSECTICIDE RESISTANCE IN ARTHROPODS
85
Hiroyoshi, T. 1977. Some new mutants and revised linkage maps of the house fly, Musca domestica
L. Jpn. J. Genet. 52:275-288.
Hughes, P. B. 1982. Organophosphorus resistance in the sheep blowfly, Lucilia cuprina (Wiede-
mann) (Oiptera: Calliphoridae): A genetic study incorporating synergists. Bull. Entomol. Res.
72:573-582.
Hughes, P. B., P. E. Green, and K. G. Reichmann. 1984. A specific resistance to malathion in
laboratory and field populations of the Australian sheep blowfly, Lucilia cuprina. J. Econ. En-
tomol. 77:1400-1404.
Judson, H. F. 1979. The Eighth Day of Creation. New York: Simon and Schuster.
Kadous, A. A., F. Matsumura, J. G. Scott, and K. Tanaka. 1983. Difference in the picrotoxinin
receptor between the cyclodiene-resistant and susceptible strains of the German cockroach. Pestic.
Biochem. Physiol. 19:157-166.
Kikkawa, H. 1964a. Genetical analysis on the resistance to parathion in Drosophila melanogaster.
II. Induction of a resistance gene from its susceptible allele. Botyu-Kagaku 2:37-41.
Kikkawa, H. 1964b. Genetical studies on the resistance to Sevin in Drosophila melanogaster. Botyu-
Kagaku 29:42-46.
Levin, B. R. 1984. Science as a way of knowing Molecular evolution. Am. Zool. 24:451-464.
Lund, A. E., and T. Narahashi. 1981a. Modification of sodium channel kinetics by the insecticide
tetramethrin in crayfish giant axons. Neurotoxicology 2:213-229.
Lund, A. E., and T. Narahashi. 1981b. Kinetics of sodium channel modification by the insecticide
tetramethrin in squid axon membranes. Pharmacol. Exp. Ther. 219:464-473.
Metcalf, R. L., and R. A. Metcalf. 1984. Steric, electronic, and polar parameters that affect the
toxic actions of O-alkyl, O-phenyl phosphorothionate insecticides. Pestic. Biochem. Physiol.
22:169-177.
Moldenke, A. F., and L. C. Terriere. 1981. Cytochrome P450 in insects. 3. Increase in substrate
binding by microsomes from phenobarbital-induced houseflies. Pestic. Biochem. Physiol. 16:222-
230.
Moore, J. A. 1984. Science as a way of knowing Evolutionary biology. Am. Zool. 24:467-534.
Nebert, D. W., M. Negishi, M. A. Lang, L. M. Hjelmeland, and J. J. Eisen. 1982. The Ah locus,
a multigene family necessary for survival in a chemically adverse environment: Comparison with
the immune system. Adv. Genet. 21:1-52.
Oppenoorth, F. J. 1982. Two different paraoxon-resistant acetylcholinesterase mutants in the house
fly. Pestic. Biochem. Physiol. 18:26-27.
Oppenoorth, F. J. 1984. Biochemistry of insecticide resistance. Pestic. Biochem. Physiol. 22:187-
193.
Ottea, J. A., and F. W. Plapp, Jr. 1981. Induction of glutathione S-aryl transferase by phenobarbital
in the house fly. Pestic. Biochem. Physiol. 15:10-13.
Ottea, J. A., and F. W. Plapp, Jr. 1984. Glutathione S-transferase in the house fly: Biochemical
and genetic changes associated with induction and insecticide resistance. Pestic. Biochem. Physiol.
22:203-208.
Paigen, K. 1979. Acid hydrolases as models of genetic control. Annul Rev. Genet. 13:417-466.
Phillips, I. R., E. A. Shephard, B. R. Rabin, R. M. Bayney, S. F. Pike, A. Ashworth, and M. R.
Estall. 1983. Factors controlling the expression of genes coding for drug-metabolizing enzymes.
Biochem. Soc. Trans. 11 :460-463.
Plapp, F. W., Jr. 1976. Chlordimeform as a synergist for insecticides against the tobacco budworm.
J. Econ. Entomol. 69:91-92.
Plapp, F. W., Jr. 1979. Synergism of pyrethroid insecticides by formamidines. J. Econ. Entomol.
72:667-670.
Plapp, F. W., Jr. 1984. The genetic basis of insecticide resistance in the house fly: Evidence that
a single locus plays a major role in metabolic resistance to insecticides. Pestic. Biochem. Physiol.
22:194-201.
86
MECHANISMS OF RESISTANCE TO PESTICIDES
Plapp, F. W., Jr., and T. C. Wang. 1983. Genetic origins of insecticide resistance. Pp. 47-70 in
Pest Resistance to Pesticides, G. P. Georghiou and T. Saito, eds. New York: Plenum.
Plapp, F. W., Jr., L. G. Tale, and E. Hodgson. 1976. Biochemical genetics of oxidative resistance
to diazinon in the house fly. Pestic. Biochem. Physiol. 6:175-182.
Rajakulendran, S. V., and F. W. Plapp, Jr. 1982. Synergism of five synthetic pyrethroids by
chlordimeform against the tobacco budworm and a predator, Chrysopa carnea. J. Econ. Entomol.
75: 1089-1092.
Ranasinghe, L. E., and G. P. Georghiou. 1979. Comparative modification of insecticide-resistance
spectrum of Culex pipiens fatigans Wied. by selection with temephos and temephos/synergist
combinations. Pestic. Sci. 10:502-508.
Sawicki, R. M. 1970. Interaction between the factor delaying penetration of insecticides and the
desethylation mechanism of resistance in organophosphorus-resistant house flies. Pestic. Sci. 1 :84-
87.
Tanaka, K., J. G. Scott, and F. Matsumura. 1984. Picrotoxinin receptor in the central nervous
system of the American cockroach: Its role in the action of cyclodiene-type insecticides. Pestic.
Biochem. Physiol. 22:117-127.
Tsukamoto, M. 1969. Biochemical genetics of insecticide resistance in the house fly. Residue Rev.
25:289-314.
Tsukamoto, M. 1983. Methods of genetic analysis of insecticide resistance. Pp. 71-98 in Pest
Resistance to Pesticides, G. P. Georghiou and T. Saito, eds. New York: Plenum.
Wang, T. C., and F. W. Plapp, Jr. 1980. Genetic studies on the location of a chromosome II gene
conferring resistance to parathion in the house fly. J. Econ. Entomol. 73:200-203.
Whitten, M. J., and J. A. McKenzie. 1982. The genetic basis for pesticide resistance. Pp. 1016 in
Proc. 3rd Australas. Conf. Grassl. Invert. Ecol., K. E. Lee, ed. Adelaide, Australia: S.A.
Government Printer.
Yamamoto, I., Y. Takahashi, and N. Kyomura. 1983. Suppression of altered acetylcholinesterase
of the green rice leafhopper by N-propyl and N-methyl carbamate combinations. Pp. 579-594 in
Pest Resistance to Pesticides, G. P. Georghiou and T. Saito, eds. New York: Plenum.
Yu, S. J. 1984. Interactions of allelochemicals with detoxification enzymes of insecticide-susceptible
and resistant fall armyworm. Pestic. Biochem. Physiol. 22:60-68.
