| Abstract
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Although P. citrinum contamination is most commonly associated with colder climates, a thermotolerant strain of this fungus was isolated from peanuts collected in the peanut growing regions of Senegal, West Africa. The P. citrinum culture filtrate resulted in significant inhibition of (H) thymidine incorporation into DNA using the in vitro lymphocyte blastogenesis assay with concanavalin A, phytohemagglutinin, and lipopolysaccharide as mitogens. P. citrinum culture filtrate (0.2 ml) administered to mice by gavage every other day for 10 days, did not significantly alter immune function. However, a challenge with Listeria monocytogenes resulted in a higher infection rate in treated mice compared to nontreated controls, which indicated a cell-mediated type immune alteration. A bacterial sensitivity test was used during the fractionation and isolation of the immunotoxic compound, which was chemically identified as ((3R-trans)-4,6-dihydro-8-hydroxy-usd 3,4,5usd-trimethyl-6-oxo-3H-2-benzopyran-7-carboxylic acid), or citrinin (and confirmed by capillary GC/quadrupole mass spectrometry and Fourier Transform IR). Subsequent studies with authentic citrinin resulted in a predictable immunotoxic response. Citrinin (the active compound of the P. citrinum culture filtrate) is fetotoxic and embryocidal in mice and rats. At higher doses, it elicits mild teratogenic effects in rats and chicken embryos. Studies were designed to experimentally assess the developmental toxicity of citrinin using Hydra attenuata (HA) (for prediction) and postimplantation rat whole embryo culture (WEC) (for confirmation). Results from the HA assay indicated that the minimal affective concentrations of citrinin required to elicit a toxic response in the adult hydra (MAC-A) and developing hydra embryo (MAC-D) were 30 and 20 mg/l, respectively. The developmental hazard index (A/D ratio) was equal to 1.5, classifying citrinin as a co-effective agent. In the WEC assay, results indicated a concentration-dependent reduction in yolk sac diameter, crown-rump length, somite number count, protein and DNA content. No gross malformations were observed. The findings suggested that citrinin is mainly embryolethal and embryotoxic: both HA and WEC assays predicted that citrinin is not a primary teratogen.
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