Differential Genes Expression Analysis of Chronic Toxicity of Organophosphorus Pesticide at Low Dose Exposure Using Oligonucleotide Microarrays

摘要

[Objective] To investigate molecular mechanism for chronic of toxicitiy organophosphorus pesticide at low level exposure. [Methods] Using Affymetrix genechip to analysis differential genes expression and pathology induced by triazophos for 12 month chronic toxicity study in ras. [Results] The tested animals were without any clinical manifestation of organophosphorus pesticide poisoning. Average dose of triazophos was 5.21 mg·kg~(-1)·d~(-1) calculated from the highest constant diet concentration of 100mg/kg at 6 months . There were 30 genes and expressed sequence tag that were differentially expressed ( with a minimum of twofold change) between treated and control groups. The differentially expressed genes include metabolism enzymes and immune response-related genes, DNA damage repair genes, stress response genes and genes of membrane proteins. Phase Ⅰ enzyme p450 2C13 and phase Ⅱ enzymes GSTA2, SULTLE2 were up-regulated., IL1B, HSPB1 were down-regulated. Average dose of triazophos was 3.86 and 0.11 mg. ·kg~(-1)· d~(-1) calculated from constant diet concentration of 100 and 3 mg/kg at 12 months treatment. Self-Organizing Map (SOM) clustering algorithm showed 184 expressed genes increased linearly in dose-response relationship and 145 expressed genes decreased adversely. Cell structure components changes were found with pathological examination. [Conclusion] The mechanism of chronic organophosphorus pesticides poisoning differs from acute. Some candidate genes may be used as biomarkers of chronic organophosphorus pesticides poisoning and treatments.