Toxicity of penicillic acid for rat alveolar macrophages in vitro

Penicillic acid (PA) is a polyketide mycotoxin produced by several species of Aspergillus and Penicillium. This mycotoxin is toxic in experimental Animals and has also been reported to be carcinogenic. The cytotoxicity of penicillic acid was studied in rat alveolar macrophages (AM) in vitro. The effects of penicillic acid on membrane integrity were studied by measuring cell volume changes and 51Cr release. There was significant 51Cr release after 2 hr exposure to 1.0 mM penicillic acid, but not after 1 hr exposure. There was a significant decrease in adenosine triphosphate (ATP) in cell cultures exposed to 1.0 mM penicillic acid for 4 hr. Inhibition of the incorporation of [3H]leucine into protein was both dose- and time-dependent and protein synthesis was inhibited significantly after 2 hr exposure to greater than or equal to 0.1 mM penicillic acid. RNA synthesis was inhibited to a lesser extent than protein synthesis. Although there was a significant inhibition of RNA synthesis at 1.0 mM PA after 4 hr, there was no inhibition of RNA synthesis even after 4 hr at any concentration less than 1.0 mM. The ED50 dose after 2 hr exposure was 0.18 and 0.60 mM for protein and RNA synthesis, respectively. There was significant inhibition of phagocytosis after 2 hr exposure at greater than or equal to 0.3 mM penicillic acid and the ED50 for phagocytosis was 0.09 mM. Thus phagocytosis was more sensitive to the toxic effects of penicillic acid than any Other cellular process studied. The results reported in this study are similar to those observed for patulin in an earlier study from our laboratory except that patulin was generally more toxic to alveolar macrophages than penicillic acid. The data demonstrate that penicillic acid is toxic to rat alveolar macrophages in vitro and suggest the possibility of a respiratory hazard to agricultural workers exposed to contaminated grain.