title: Comparative toxicity of four microcystins of different hydrophobicities to the protozoan, Tetrahymena pyriformis.
abstract: Microcystins (MC) are a group of over 60 cyclic heptapeptide hepatotoxins produced by cyanobacteria. The 1-octanol/water partition coefficients (log P) of MC-LR, -LY, -LW and -LF have been estimated by HPLC to be 2.16, 2.92, 3.46 and 3.56, respectively. Their in vivo toxicities to Tetrahymena pyriformis was also investigated. Twenty-four hour LC50 values followed the order MC-LR > -LY > -LW approximately -LF. The LC50 values of MC-LR and -LY were significantly reduced in the presence of 1% (v/v) dimethylsulphoxide, although no significant effect occurred with MC-LW or -LF. Tetrahymena pyriformis respiration rates were inhibited by MC-LR in both a time- and dose-dependent manner. Increasing log P of the MC used caused a significantly greater inhibition of respiration. Population growth rate and maximum culture density were inhibited by all MC variants in proportion to log P. Positive correlations between all toxicological endpoints and log P occurred, with the most hydrophobic toxin, MC-LF, being 1.4 to 3.5 times more toxic than MC-LR. MC-LW had a similar toxicity to MC-LF, while MC-LY toxicity was intermediate between that of MC-LR and -LF. Implications of this positive relationship between in vivo toxicity and hydrophobicity for the toxicity of MC to aquatic organisms, and the potential for using log P as a descriptor in a quantitative structure-activity relationship for MC, are discussed.
authors.affiliation: Department of Biological Sciences, University of Dundee, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Ward
authors.forename: G A
authors.initials: GA
authors.lastname: Codd
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D000458:Cyanobacteria / Q000737:chemistry*; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic / Q000633:toxicity; D012995:Solubility; D013769:Tetrahymena pyriformis / Q000187:drug effects*
chemical_list: D001427:Bacterial Toxins; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C084459:microcystin LY; C057862:cyanoginosin LR