title: In vitro and in vivo mutagenicity studies on sporidesmin, the toxin associated with facial eczema in ruminants.
abstract: Sporidesmin, a fungal toxin with widespread distribution within New Zealand, is thought to exert toxic effects through oxidative damage. The purified chemical was tested for its ability to cause point mutations in four strains of Salmonella typhimurium (TA98, TA100, TA102 and TA1537), in the presence and absence of exogenous metabolic activation. Although toxic effects were seen at concentrations exceeding 400 mu gl/plate, there were no significant increases in revertant colonies. In strain TA102, these results were not modified by the presence of glutathione. In AA8 Chinese hamster cells, sporidesmin acted as a potent clastogen, causing chromosomal breaks at concentrations as low as 3 ng/ml, where there was very little reduction in cell viability. Effects were primarily at the chromatid level, but some chromosomal events were also seen. Following low doses, the most common events were chromatid deletions and induction of double minute chromosomes. Interchange events occurred at concentrations of 10 ng/ml and above. The most common of these events was an incomplete chromatid interchange, although some examples of complete chromatid and chromosomal interchange were seen. These in vitro experiments were subsequently extended to an in vivo study of sporidesmin-induced lymphocytic micronuclei (MN) in sheep. In a double blind experiment, 5 sheep were treated with a single high dose of sporidesmin. Blood samples were taken from these, and from 5 untreated sheep, at various intervals before and after treatment. Peripheral blood lymphocytes cultures were harvested and scored for MN in cytokinesis-blocked cells, as a measure of clastogenic activity of sporidesmin in vivo. Following decoding, statistical analysis of the data revealed no significant differences between the MN levels in peripheral blood lymphocytes of sporidesmin-treated and untreated sheep. Although the possibility still exists that clastogenic effects could occur in other species, the data indicate that sporidesmin is not a clastogen in sheep, even though this species is highly susceptible to the toxic effects of sporidesmin.
authors.affiliation: Cancer Research Laboratory, University of Auckland Medical School, Private Bag, New Zealand.
authors.forename: L R
authors.initials: LR
authors.lastname: Ferguson
authors.forename: J
authors.initials: J
authors.lastname: Berriman
authors.forename: A
authors.initials: A
authors.lastname: Pearson
authors.forename: R
authors.initials: R
authors.lastname: Munday
authors.forename: E A
authors.initials: EA
authors.lastname: Fowke
authors.forename: N R
authors.initials: NR
authors.lastname: Towers
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002842:Chromatids / Q000187:drug effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004485:Eczema / Q000662:veterinary; D048629:Micronuclei, Chromosome-Defective; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009154:Mutation; D012486:Salmonella typhimurium; D012756:Sheep; D012757:Sheep Diseases; D013173:Sporidesmins
chemical_list: D013173:Sporidesmins