2 SIGNIFICANT ASPECTS OF MICROCYSTIN-LR - SPECIFIC BINDING AND LIVER SPECIFICITY

Microcystin-LR is a unique and potent liver tumor promoter, belonging to the okadaic acid class compounds. Although microcystin-LR is a pote nt inhibitor of protein phosphatases 1 and 2A, as is okadaic acid, mic rocystin-LR has liver specificity dominance. Two significant aspects, specific binding and liver specificity of [H-3]dihydromicrocystin-LR, a reduced form of microcystin-LR, were studied and compared with those of [H-3]okadaic acid. [H-3]-Dihydromicrocystin-LR had higher affinity for the receptors in both the particulate and cytosolic fractions of rat liver and various tissues than had [H-3]okadaic acid. Intraperiton eal administration of [H-3]dihydrdmicrocystin-LR into mice resulted in the highest uptake into the liver, 71.5 +/- 6.9% of the total adminis tered radioactivity, whereas p.o. administration resulted in less than 1% uptake into the liver, suggesting that the mechanisms of the incor poration of microcystin-LR into the liver by i.p. and p.o. administrat ions are greatly different. The presence of associated forms of [H-3]d ihydromicrocystin-LR with macromolecules in the liver indicates a need for further investigation.