Altering cytochrome P4501A activity affects polycyclic aromatic hydrocarbon metabolism and toxicity in rainbow trout (Oncorhynchus mykiss).
The polycyclic aromatic hydrocarbons (PAHs) phenanthrene and retene (7-isopropyl-1-methyl phenanthrene) are lethal to rainbow trout (Oncorhynchus mykiss) larvae during chronic exposures. Phenanthrene is a low-toxicity, non-cytochrome P4501A (CYP1A)-inducing compound that accumulates in fish tissues during exposure to lethal concentrations in water. Retene is a higher toxicity CYP1A-inducing compound that is not detectable in tissue at lethal exposure concentrations. The metabolism, excretion, and toxicity of retene and phenanthrene were examined in juvenile and larval rainbow trout during coexposure to the model CYP1A inducer beta-naphthoflavone (betaNF), or to the inducer-inhibitor piperonyl butoxide to determine if modulating CYP1A activity affected PAH metabolism and toxicity. Phenanthrene metabolism, excretion rate, and toxicity increased with coexposure to betaNE Piperonyl butoxide inhibited phenanthrene metabolism and reduced the excretion of all phenanthrene metabolites. As a consequence, embryo mortality rates increased but rates of sublethal effects did not. Coexposure of trout to retene and betaNF caused no change in retene metabolism and excretion, but retene toxicity increased, perhaps due to additivity. Piperonyl butoxide inhibited retene metabolism, decreased the excretion of some retene metabolites while increasing the excretion of others, and increased the toxicity of retene. These results support the role of CYP1A activity in PAH metabolism and excretion, and the role ofthe CYP1A-generatedmetabolites of PAHs in chronic toxicity to larval fish.
School of Environmental Studies, Queen's University, Kingston, Ontario, Canada.
Stephanie A
SA
Hawkins
Sonya M
SM
Billiard
Samir P
SP
Tabash
R Stephen
RS
Brown
Peter V
PV
Hodson
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007814:Larva; D017686:Oncorhynchus mykiss / Q000502:physiology*; D010574:Pesticide Synergists / Q000494:pharmacology; D010616:Phenanthrenes / Q000378:metabolism* / Q000633:toxicity*; D010882:Piperonyl Butoxide / Q000494:pharmacology; D014018:Tissue Distribution; D014874:Water Pollutants, Chemical / Q000378:metabolism* / Q000633:toxicity*; D019324:beta-Naphthoflavone / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010574:Pesticide Synergists; D010616:Phenanthrenes; D014874:Water Pollutants, Chemical; C447880:retene; C031181:phenanthrene; D019324:beta-Naphthoflavone; D001189:Aryl Hydrocarbon Hydroxylases; D010882:Piperonyl Butoxide