penicillic acid :
| 13: Environ Res 1986 Dec;41(2):505-13 |
|
Toxicity of penicillic acid for rat alveolar macrophages
in vitro.
Sorenson WG, Simpson J.
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.
PMID: 2430790
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