Molecular cloning of a family of xenobiotic-inducible drosophilid cytochrome P450s: Evidence for involvement in host-plant allelochemical resistance

Danielson, Phillip B.; MacIntyre, Ross J.; Fogleman, James C.

doi:10.1073/pnas.94.20.10797

Cited by 113 publications

(65 citation statements)

References 32 publications

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“…In Drosophila, selective selection occurs of strains living in, for example, the area of the Senita Cactus secreting toxic isoquinoline alkaloids and only the Drosophila mettleri but no Drosophila melanogaster strain is surviving in this area because their ability to induce CYP6 and CYP28. 38 An interesting genetic selection also occurs in Drosophila being resistant to insecticides. From 1930 to 1960, insecticide resistant stains have rapidly evolved.…”

Section: Cyp2d6 Genetic Polymorphismmentioning

confidence: 99%

Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity

2004

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CYP2D6 is of great importance for the metabolism of clinically used drugs and about 20-25% of those are metabolised by this enzyme. In addition, the enzyme utilises hydroxytryptamines as endogenous substrates. The polymorphism of the enzyme results in poor, intermediate, efficient or ultrarapid metabolisers (UMs) of CYP2D6 drugs. It is plausible that the UM genotype, where more than one active gene on one allele occurs, is the outcome of selective dietary selection in certain populations in North East Africa. The UM phenotype affects 5.5% of the population in Western Europe. A hypothesis for the evolutionary basis behind selection for CYP2D6 gene duplications is presented in relation to selection for Cyp6 variants in insecticide resistant Drosophila strains. The polymorphism of CYP2D6 significantly affects the pharmacokinetics of about 50% of the drugs in clinical use, which are CYP2D6 substrates. The consequences of the polymorphism at ordinary drug doses can be either adverse drug reactions or no drug response. Examples are presented where CYP2D6 polymorphism affects the efficacy and costs of drug treatment. Predictive CYP2D6 genotyping is estimated by the author to be beneficial for treatment of about 30-40% of CYP2D6 drug substrates, that is, for about 7-10% of all drugs clinically used, although prospective clinical studies are necessary to evaluate the exact benefit of drug selection and dosage based on the CYP2D6 genotype.

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Section: Cyp2d6 Genetic Polymorphismmentioning

confidence: 99%

Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity

2004

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“…In the following, we highlight selected pharmacogenomic examples that impact clinical practice and refer to the primary references provided in Tables 2 and 3 as well as to comprehensive recent reviews for further information on the topic [49][50][51]. Resistance developed due to induction of these genes [13] Fruit fly (Drosophila melanogaster) CYP6G1 DDT Amplification of the CYP6G1 gene causes insecticide resistance [14] Green house whitefly (Trialeurodes vaporariorum)…”

Section: Pharmacogenomic Germline Biomarkersmentioning

confidence: 99%

Pharmacogenomic Biomarkers for Improved Drug Therapy—Recent Progress and Future Developments

Lauschke

Milani

Ingelman‐Sundberg

2017

AAPS J

107

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Abstract.Much of the inter-individual variability in drug efficacy and risk of adverse reactions is due to polymorphisms in genes encoding proteins involved in drug pharmacokinetics and pharmacodynamics or immunological responses. Pharmacogenetic research has identified a multitude of gene-drug response associations, which have resulted in genetically guided treatment and dosing decisions to yield a higher success rate of pharmacological treatment. The rapid technological developments for genetic analyses reveal that the number of genetic variants with importance for drug action is much higher than previously thought and that a true personalized prediction of drug response requires attention to millions of rare mutations. Here, we review the evolutionary background of genetic polymorphisms in drugmetabolizing enzymes, provide some important examples of current use of pharmacogenomic biomarkers, and give an update of germline and somatic genome biomarkers that are in use in drug development and clinical practice. We also discuss the current technology development with emphasis on complex genetic loci, review current initiatives for validation of pharmacogenomic biomarkers, and present scenarios for the future taking rare genetic variants into account for a true personalized genetically guided drug prescription. We conclude that pharmacogenomic information for patient stratification is of value to tailor optimized treatment regimens particularly in oncology. However, the routine use of pharmacogenomic biomarkers in clinical practice in other therapeutic areas is currently sparse and the prospects of its future implementation are being scrutinized by different international consortia.

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“…Insect P450s capable of metabolizing allelochemicals have been identified (30,31). For example, CYP6B1v1 and CYP6B3v1 from the black swallowtail butterfly, Papilio polyxenes, can metabolize the furanocoumarins it is exposed to in its diet (32,33).…”

mentioning

confidence: 99%

Characterization of Drosophila melanogaster cytochrome P450 genes

Chung

Sztal

Pasricha

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

249

229

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Cytochrome P450s form a large and diverse family of hemecontaining proteins capable of carrying out many different enzymatic reactions. In both mammals and plants, some P450s are known to carry out reactions essential for processes such as hormone synthesis, while other P450s are involved in the detoxification of environmental compounds. In general, functions of insect P450s are less well understood. We characterized Drosophila melanogaster P450 expression patterns in embryos and 2 stages of third instar larvae. We identified numerous P450s expressed in the fat body, Malpighian (renal) tubules, and in distinct regions of the midgut, consistent with hypothesized roles in detoxification processes, and other P450s expressed in organs such as the gonads, corpora allata, oenocytes, hindgut, and brain. Combining expression pattern data with an RNA interference lethality screen of individual P450s, we identify candidate P450s essential for developmental processes and distinguish them from P450s with potential functions in detoxification.detoxification genes ͉ in situ hybridization ͉ insecticide resistance ͉ multigene family ͉ RNAi

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Molecular cloning of a family of xenobiotic-inducible drosophilid cytochrome P450s: Evidence for involvement in host-plant allelochemical resistance

Cited by 113 publications

References 32 publications

Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity

Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity

Pharmacogenomic Biomarkers for Improved Drug Therapy—Recent Progress and Future Developments

Characterization of Drosophila melanogaster cytochrome P450 genes

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