title: Characterization of chemically tritiated microcystin-LR and its distribution in mice.
abstract: Chemically tritiated microcystin-LR (spec. act. 194 mCi/mmol), purified to greater than 95% by C-18 reverse-phase high performance liquid chromatography, exhibited the same retention time and ultraviolet absorption profile as unlabeled toxin. Acid-hydrolyzed [3H]-toxin yielded tritiated glutamate and beta-methylasparate. Stability of the nonexchangeable [3H]-toxin in saline and urine was greater than 93% after 42 days stored at 22 degrees, 4 degrees or -20 degrees C. In blood, the breakdown of toxin was temperature- and time-dependent (63% at 22 degrees C, 28 days). Unlabeled toxin was stable for greater than 42 days stored at either 4 degrees or -20 degrees C in saline. The LD50 (mouse, i.p.) of [3H]-microcystin-LR and unlabeled toxin was the same [75 micrograms/kg (65-90) and 65 micrograms/kg (53-80), respectively]. From 3 to 90 min after i.p. injection of 70 micrograms/kg [3H]-microcystin-LR there was a slow absorption of toxin from the peritoneal cavity and efficient accumulation in liver. The elimination half-life of the plasma concentration curve was 29 min. Tritium distribution in tissue at death or 6 hr post injection was similar for all doses (13-101 micrograms/kg). At 101 micrograms/kg, liver contained 56 +/- 1%, intestine 7 +/- 1%, kidney 0.9 +/- 0.2% and carcass 10 +/- 1% of the injected dose. Heart, spleen, lung and skeletal muscle contained less than 1% of the radiolabel.
authors.affiliation: Pathophysiology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, Frederick, MD 21701-5011.
authors.forename: N A
authors.initials: NA
authors.lastname: Robinson
authors.forename: G A
authors.initials: GA
authors.lastname: Miura
authors.forename: C F
authors.initials: CF
authors.lastname: Matson
authors.forename: R E
authors.initials: RE
authors.lastname: Dinterman
authors.forename: J G
authors.initials: JG
authors.lastname: Pace
mesh_terms: D000818:Animals; D001427:Bacterial Toxins; D002851:Chromatography, High Pressure Liquid; D000458:Cyanobacteria; D000087522:Cyanobacteria Toxins; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007553:Isotope Labeling; D007928:Lethal Dose 50; D008297:Male; D008387:Marine Toxins / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D052998:Microcystins; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D014316:Tritium
chemical_list: D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D014316:Tritium; C057862:cyanoginosin LR