Master of Science (MSc)
Faculty of Science
The pesticide, 3-trifluoromethyl-4-nitrophenol (TFM), has been extensively used over the last 50 years to control invasive sea lamprey (P. marinus) populations in the Great Lakes, but its mechanism of toxicity is unresolved. Due to its structural similarity to phenolic compounds known to inhibit mitochondrial ATP production, one hypothesis on the mode of action of TFM is that it impairs mitochondrial oxidative phosphorylation. A second hypothesis is that TFM targets the gill, interfering with gill ion uptake. Exposure of larval sea lamprey and rainbow trout (O. mykiss), to each animal’s respective 12-h TFM LC50, resulted in marked disturbances to internal fuel stores, but not ion balance. In the brain and liver, glycogen levels decreased by more than 50% in both species in response to TFM exposure, suggesting that a mismatch between ATP supply and ATP demand occurred. These findings support the hypothesis that death in lamprey and trout exposed to TFM is due to a depletion of ATP and ATP-generating fuels (glycogen). Experiments with isolated mitochondria demonstrated that TFM uncouples mitochondrial oxidative phosphorylation. Impairment of mitochondrial oxidative ATP production was most likely the result of TFM-induced reductions in the proton-motive force, which is needed to drive H+ flow through the ATP-synthase. In lamprey, TFM caused no disturbances in Na+ uptake, suggesting that it does not compromise lamprey gill function. In trout, TFM exposure resulted in a 60% reduction in Na+ uptake, which may have been caused by a shortfall in ATP supply for gill Na+/K+ ATPases. The knowledge that TFM uncouples mitochondrial oxidative phosphorylation and the effects that it has on energy stores in lamprey and trout could help better predict target and non-target sensitivity to TFM.
Birceanu, Oana, "Mechanism(s) of 3-Trifluoromethyl-4-Nitrophenol (TFM) Toxicity in Sea Lamprey (Petromyzon marinus) & Rainbow Trout (Oncorhynchus mykiss)" (2009). Theses and Dissertations (Comprehensive). 927.