Does the Clock Make the Poison? Circadian Variation in Response to Pesticides

Abstract

BackgroundCircadian clocks govern daily physiological and molecular rhythms, and putative rhythms in expression of xenobiotic metabolizing (XM) genes have been described in both insects and mammals. Such rhythms could have important consequences for outcomes of chemical exposures at different times of day. To determine whether reported XM gene expression rhythms result in functional rhythms, we examined daily profiles of enzyme activity and dose responses to the pesticides propoxur, deltamethrin, fipronil, and malathion.Methodology/Principal FindingsPublished microarray expression data were examined for temporal patterns. Male Drosophila were collected for ethoxycoumarin-O-deethylase (ECOD), esterase, glutathione-S-transferase (GST), and, and uridine 5′-diphosphoglucosyltransferase (UGT) enzyme activity assays, or subjected to dose-response tests at four hour intervals throughout the day in both light/dark and constant light conditions. Peak expression of several XM genes cluster in late afternoon. Significant diurnal variation was observed in ECOD and UGT enzyme activity, however, no significant daily variation was observed in esterase or GST activity. Daily profiles of susceptibility to lethality after acute exposure to propoxur and fipronil showed significantly increased resistance in midday, while susceptibility to deltamethrin and malathion varied little. In constant light, which interferes with clock function, the daily variation in susceptibility to propoxur and in ECOD and UGT enzyme activity was depressed.Conclusions/SignificanceExpression and activities of specific XM enzymes fluctuate during the day, and for specific insecticides, the concentration resulting in 50% mortality varies significantly during the day. Time of day of chemical exposure should be an important consideration in experimental design, use of pesticides, and human risk assessment.

Esterase-based metabolic resistance to insecticides in heliothine and spodopteran pests

“…123,124) There are also data showing coordinate control of some esterase, P450 and GST genes mediated by circadian clock genes, with correlated effects on xenobiotic (including permethrin) detoxification. [124][125][126] It is clearly unlikely that circadian clock genes are directly involved in the resistance phenotypes we have reviewed. However these and the microarray data demonstrate that the expression of at least some genes with primary detoxification functions are embedded in larger regulatory networks.…”

Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae

“…gambiae likely translates into rhythmic patterns of time-of-day susceptibility to insecticide, as found in numerous insects including the mosquito Ae. aegypti (63,64). Interestingly, the metabolic detoxifying genes we identified do not cluster uniformly in time of peak expression.…”

Genomic Differentiation Between Temperate and Tropical Australian Populations ofDrosophila melanogaster

“…Ace codes for an acetylcholinesterase associated with pesticide resistance (Menozzi et al 2004), which was previously identified as a differentiated CNV between these populations (Turner et al 2008). Interestingly, Ace expression has been shown to vary over the circadian cycle (Hooven et al 2009), and acetylcholinesterase levels are highly correlated with pesticide resistance (Charpentier and Fournier 2001).…”