Dataset Information

Multigene biomarkers of pyrethroid exposure: preliminary experiments: 15k microarrays

ABSTRACT: We describe initial development of RNA profiling-based assays for detecting pyrethroid pesticides in water. We conducted 48-hour flow-through exposures of Pimephales promelas adults and larvae to lab water and eight nominal concentrations of each of four pyrethroid insecticides: bifenthrin, cypermethrin, esfenvalerate, and (trans) permethrin. Concentration-response curves suggest steep dose responses, and LC50s below most published values. Expression microarray analysis of dissected brains from adults and whole larvae exposed to cypermethrin and bifenthrin suggests both assay formats can be used to detect these pyrethroids at concentrations well below P. promelas LC50s, and below LC50s of about 70% of aquatic metazoan species. Geneset analysis and intersections between lists of differentially expressed genes failed to identify substantial functional overlaps between these toxicants. Geneset analysis was sensitive to parameter choice, which may reflect the large number of genes analyzed relative to the number of samples, and substantial biological variability relative to effect sizes. Several identified GO terms can be rationalized based on known pyrethroid action, but implications of other highlighted GO terms are unclear.

ORGANISM(S): Pimephales promelas

PROVIDER: GSE113284 | GEO | 2018/10/31

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Aedes aegypti SP strain vs. SMK strain. Aedes aegypti is the major vector of yellow fever and dengue/dengue hemorrhagic fever. Starting with a population collected from Singapore, we established a pyrethroid-resistant A. aegypti strain (SP) and investigated three major possible mechanisms of insecticide resistance. After 10 generations of adult selection, an A. aegypti strain developed 1650-fold resistance to permethrin, which is one of the most widely used pyrethroid insecticides for mosquito control. SP larvae also developed 8790-fold resistance following selection of the adults. Prior to the selections, the frequencies of V1016G and F1534C mutations in domains II and III, respectively, of voltage-sensitive sodium channel genes (Vssc) were 0.44 and 0.56, respectively. In contrast, only G1016 alleles were present after two permethrin selections, indicating that G1016 can contribute more to the insensitivity of Vssc than C1534. In vivo metabolism studies showed that the SP strain excreted permethrin metabolites more rapidly than the susceptible SMK strain. Pretreatment with piperonyl butoxide caused strong inhibition of excretion of permethrin metabolites, suggesting that cytochrome P450 monooxygenases (P450s) play an important role in resistance development. In vitro metabolism studies also indicated an association of P450s with resistance. Microarray analysis showed that multiple P450 genes were over-expressed during the larval and adult stages in the SP strain. Following quantitative real time PCR, we focused on two P450 isoforms, CYP9M6 and CYP6BB2, and confirmed that they were capable of detoxifying permethrin to 4'-HO-permethrin. Over-expression of CYP9M6 was partially due to gene amplification. Association analysis demonstrated that CYP9M6 and CYP6BB2 complementarily conferred permethrin resistance. Two other P450s (CYP9J26 and CYP9J28), which are capable of metabolizing permethrin, were also over-expressed in the SP strain, indicating that at least four P450 isoforms are likely involved in resistance development. Our data show that it is unlikely that reduced cuticle penetration of permethrin contributes to resistance. One-color experiment with two strains (SP, SMK) and 3 developmental stages/genders (larvae, adult males, and adult females), 4 biological replicates each.

Dataset Information

Multigene biomarkers of pyrethroid exposure: preliminary experiments: 15k microarrays

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure