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1 Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom
2 Department of Biochemistry & Biology, University of Bath, Bath, United Kingdom
3 Veterinary Medicine Research and Development, Pfizer Animal Health, Sandwich, United Kingdom
4 Molecular Genetics, University of Glasgow, United Kingdom; Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom
5 School of Biological Sciences, University of Exeter, United Kingdom
* To whom correspondence should be addressed. E-mail: j.a.t.dow{at}bio.gla.ac.uk.
Insecticide resistance is a major problem for both medicine and agriculture, and is frequently associated with over-expression of metabolic enzymes that catalyse the breakdown of pesticides, leading to broad-spectrum resistance. However the insect tissues within which these metabolic enzymes normally reside remain unclear. Microarray analysis of 9 adult tissues from Drosophila melanogaster reveals that cytochrome P450s and glutathione-S-transferases show highly tissue-specific expression patterns; most were confined to one or more epithelial tissues, and half showed dominant expression in a single tissue. The particular detoxifying enzymes encountered by a xenobiotic thus depend critically on the route of administration. In particular, known insecticide metabolism genes are highly enriched in insect Malpighian (renal) tubules, implicating them in xenobiotic metabolism. The tubules thus display, with the fat body, roles analogous to the vertebrate liver and immune system, as well as its acknowledged renal function. To illustrate this, when levels of a single gene, Cyp6g1, were manipulated in just the Malpighian tubules of adult Drosophila, the survival of the whole insect after DDT challenge was altered, whereas corresponding manipulations in the nervous system or the fat body were without effect. This shows that, although detoxification enzymes are widely distributed, baseline protection against DDT resides primarily in the insect excretory system, corresponding to less than 0.1% of the mass of the organism.
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