UPREGULATION OF MIR-17 AND MIR-221 BY BENOMYL, CARBARYL, MALATHION AND DIAZINON PESTICIDES IN MICE BLOOD

Öz

Objective: Increasing evidence demonstrate that the expression of miRNAs is affected by several known toxicants and environmental contaminants. To evaluate the toxicity effect of the pesticides including benomyl, carbaryl, malathion, diazinon on male Balb/c mice, expression profile of two oncogenic miRNAs were analysed by real-time PCR.

Material and Method:The 72 male mice were divided into 6 groups (n = 6 per group), including control (0 mg/kg), malathion (30 mg/kg), carbaryl (20 mg/kg), benomyl (30 mg/kg), diazinon (20 mg/kg) and mixture of all pesticides. Mice were intragastrically gavaged for 60 days, then sacrificed on the 30(th) and 60(th) day. The levels of oncogenic mir-17 and mir-221 in the serum were measured.

Result and Discussion: The results showed that compared with the normal controls, mir-17 and mir221 were overexpressed in all treatment groups during 2 months. The expression level of miR-17 and mir-221 after 60 days were 9.2-17.7 fold and 1.9-4 fold higher than the first month respectively. The lowest increase was 1.9-fold, belongs to mir-221, which is still enough for easy diagnosis. These results provide new insights into the negative pesticide’s carcinogenic probability via dysregulation of two oncogenic miRNAs. Our results suggest that due to positive association between mir-17 and mir-221 levels and the risk of toxicity, these miRNAs might be a useful biomarker in malignancy prediction and have a diagnostic value. 

Anahtar Kelimeler

• Dysregulation
• miRNA
• oncogene
• pesticides
• toxicity

FARE KANINDA MIR-17 VE MIR-221'İN BENOMİL, KARBARİL, MALATİYON VE DİAZİNON PESTİSİTLERİ İLE UPREGÜLASYONU

Öz

Amaç: Artan kanıtlar miRNA'ların ekspresyonunun bazı bilinen toksik maddeler ve çevresel kirleticiler tarafından etkilendiğini göstermektedir. Pestisitlerin toksisite etkisini değerlendirmek üzere erkek Balb/c farelerinde benomil, karbaril, malatiyon, diazinonun onkojenik miRNA ekspresyona etkisi gerçek zamanlı PCR ile analiz edildi.

Gereç ve Yöntem: 72 erkek fare 6 gruba ayrıldı: kontrol (0 mg/kg), malatiyon (30 mg/kg), karbaril (20 mg/kg), benomil (30 mg/kg) ve diazinon (20 mg/kg). Fareler 60 gün boyunca intragastrik yoldan sonda ile beslendi, daha sonra 30. ve 60. gününde öldürüldü. Serumda onkojenik mir-17 ve mir-221 düzeyleri ölçüldü.

Sonuç ve Tartışma: Sonuçlar normal kontrollerle karşılaştırıldığında, mir-17 ve mir-221 tüm tedavi gruplarında 2 ay boyunca aşırı eksprese edildiği görüldü. Mir-17 ve mir-221 ekspresyon düzeyi ilk aya göre 60 gün sonra sırasıyla 9,2-17,7 kat ve 1,9-4 kat daha yüksekti. En düşük artış 1,9 kat ile mir-221'e aittir ki, hala kolay teşhis için yeterlidir. Bu sonuçlar iki onkojenik miRNA’nın disregülasyonuyla pestisitlerin negatif karsinojenik olasılığına yeni bilgiler sağlamaktadır. Sonuçlarımız mir-17 ve mir-221 seviyeleri ve toksisite riski arasındaki pozitif ilişki nedeniyle, bu miRNA'ların malignite tahmininde yararlı bir biyobelirteç olabileceğini ve diyagnostik değeri olduğunu göstermektedir.

Anahtar Kelimeler

• Disregülasyon
• miRNA
• onkojen
• pestisitler
• toksisite

Kaynakça

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