Non-conventional biomarkers of effects for organophosphates as alternatives in an experimental model showing inherently low-levels of AChE.

SOTOMAYOR V.; VENTURINO, A

Buenos Aires

Congreso; IV Argentinian meeting of the Society of Environmental Toxicology and Chemistry, SETAC Argentina.; 2012

Society of Environmental Toxicology and Chemistry, SETAC Argentina.

This study documents alternatives to acetylcholinesterase (AChE) as biomarkers of organophosphorus (OP) toxicity, in early stages of Rhinella. arenarum embryos which lack substantial activity of this enzyme until later in development. Embryos were exposed to sublethal concentrations (2-16 mg/L) of chlorpyrifos (CPF). AChE activity, polyamine levels and their key regulator enzyme ornithine decarboxylase (ODC), as well as transcription factors and signaling kinases related to development were measured. AChE was induced by low CPF concentrations, and inhibited only at 16 mg/L. Polyamine levels were diminished at low concentrations, as well as ODC activity. Using Western blot and electromobility shift assay we studied transcription factor activator protein-1 (AP-1) pathway in our search for molecular effects in the absence of AChE activity inhibition when embryos were exposed at low CPF concentrations. AP-1 binding to its consensus sequence in DNA (CRE) and the levels of its constituent protein c-fos were decreased by CPF; c-fos activator kinase Erk-2 was also decreased. These results allow us to infer a possible pathway for CPF effects in early toad embryos, leading to alteration in the polyamine metabolism, since ODC transcription is under AP-1 regulation. We propose polyamine levels, ODC activity and some members of the AP-1 pathway, as alternative biomarkers of effects in R. arenarum embryos at tail bud stage showing low levels of AChE activity, hence lacking of the classical response to OP.