Ochratoxin A, a toxin of Aspergillus ochraceus, suppresses the immune response to sheep erythrocytes in BALB/c mice at doses as low as 0.005 pg/kg of body weight. This effect is prevented by phenylalanine. Ochratoxin A (OT-A) has been shown to inhibit protein synthesis and, to a certain extent, ribonucleic acid synthesis in bacteria (8, 14). In
Citrinin, a mycotoxin of Penicillium citrinum and other species of the genera Penicillium and Aspergillus, caused the following effects at different concentrations in Escherichia coli. In vivo at 100 ,ug/mI single-strand breaks were caused in the chromosomal DNA. In the presence of 100 ,ug/ml, UV (254 nm)-induced DNA damage was repaired in the bacterial cells without need for a complete growth medium. At 300 ,ug/ml lambda ts prophage was induced in a lysogenic E. coli strain. In an E. coli strain carrying a F' lac plasmid, 4.7% of the cells displayed the Lac-phenotype after treatment with 200 ,ug of citrinin per ml, suggesting elimination of the F' factor. In vitro, DNA repair synthesis was observed at 5 ,ug of citrinin per ml in permeabilized cells, and replicative DNA synthesis was inhibited at 200 ,ug/ml. In these systems synthesis of stable RNAs was slightly diminished at 300 ,ug/mI, and protein synthesis was not affected at concentrations up to 450 ,ug/ml. Lambda and ColEl plasmid DNA were cleaved in vitro when small amounts of copper ions were present. This DNA-attacking activity was prevented by NADPH, catalase, and superoxide dismutase and by higher concentrations of hydroxyl radical scavengers, suggesting the involvement of free radicals in the mechanism of action of citrinin on DNA.
We investigated cytoplasmic control of tumorigenicity in cybrids. Cytoplasts derived from nontumorigenic cells were fused to the highly tumorigenic 984 C1 10-15 cell line derived from a murine teratoma. The resultant cybrids did not retain the tumorigenicity of the original cell line. In addition, the majority demonstrated the ability to differentiate into skeletal muscle. The results of these experiments indicate a heritable suppression of the tumorigenic phenotype by nontumorigenic cytoplasm. These findings are in contrast to our previous experiments in which we used a different experimental system and demonstrated a nuclear control of tumorigenicity in cybrids.
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