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The Toxic Oil Syndrome (TOS) was a toxic epidemic disease, related to the consumption of rapeseed oil denatured with aniline that affected more than 20,000 people in Spain and resulted in more than 330 deaths after its sudden appearance in 1981. It has been reported that the fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP) have shown a strong association with TOS. These PAP-esters could be absorbed and metabolized in a similar way than phospholipids. This is of interest because some products of phospholipid metabolism are important mediators in downstream pathways involved in the regulation of different nuclear factors. In particular, phospholipase D activity is involved in the activation of c-fos. Thus, we have investigated the effect of different PAP-esters in the induction of c-fos in lung fibroblasts. Results indicate that PAP-esters rapidly induced the expression of c-fos in a dose–dependent manner. In addition, both butanol and propranolol prevent this induction pointing to the involvement of phospholipase D in this activation. These results suggest that deregulation of some nuclear factors such as AP-1 could be involved in the pathogenesis of TOS. [Copyright &y& Elsevier]