Microcystin-LR is not Mutagenic in vivo in the λ/lacZ Transgenic Mouse (Muta^TMMouse)

Abstract

The water pollution of toxic cyanobacteria (blue-green algae) is causing a serious public health problem in many parts of the world. Microcystin-LR (MCLR) is a potent cyclic heptapeptidic hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. MCLR presents acute and chronic hazards to human health and has been linked to primary liver cancer in humans chronically exposed to this peptide toxin through drinking water. To assess the in vivo mutagenecity of MCLR, the λ/lacZ transgenic mice (Muta^TMMouse) were treated with MCLR (1 mg/kg per week x 4) and examined for mutant frequencies (MFs) in the lacZ and cII genes of liver and lungs. Micronucleus induction in peripheral blood cells was also assessed. Co-mutagenic effect of MCLR was studied in combination with N-nitrosodiethylamine (DEN). MCLR did not increase either MFs of the target genes in liver and lungs or micronucleus frequency in the peripheral blood cells of the λ/lacZ transgenic mouse. While DEN treatment increased MFs significantly, the co-administration of MCLR did not potentiate its mutagenicity. We conclude that pure MCLR has no in vivo mutagenicity as it failed to induce gene mutation and micronucleus in transgenic mouse. Its tumor promoting effect is independent of its interaction to DNA.