Genotoxicity of microcystin-LR in human lymphoblastoid TK6 cells.
Toxic cyanobacteria (blue-green algae) water blooms have become a serious problem in several industrialized areas of the world. Microcystin-LR (MCLR) is a cyclic heptapeptidic toxin produced by the cyanobacteria. In the present study, we used human lymphoblastoid cell line TK6 to investigate the in vitro genotoxicity of MCLR. In a standard 4h treatment, MCLR did not induce a significant cytotoxic response at <80 microg/ml. In a prolonged 24h treatment, in contrast, it induced cytotoxic as well as mutagenic responses concentration-dependently starting at 20 microg/ml. At the maximum concentration (80 microg/ml), the micronucleus frequency and the mutation frequency at the heterozygous thymidine kinase (TK) locus were approximately five-times the control values. Molecular analysis of the TK mutants revealed that MCLR specifically induced loss of heterozygosity at the TK locus, but not point mutations or other small structural changes. These results indicate that MCLR had a clastogenic effect. We discuss the mechanisms of MCLR genotoxicity and the possibility of its being a hepatocarcinogen.
Zhan
Li
L
Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Sakamoto
Hiroko
H
Sakuraba
Mayumi
M
Wu
De Sheng
DS
Zhang
Li Shi
LS
Suzuki
Takayoshi
T
Hayashi
Makoto
M
Honma
Masamitsu
M
D002460:Cell Line; D006801:Humans; D008099:Liver / Q000187:drug effects; D019656:Loss of Heterozygosity; D008387:Marine Toxins; D052998:Microcystins; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D010456:Peptides, Cyclic / Q000633:toxicity*; D013937:Thymidine Kinase / Q000235:genetics
D008387:Marine Toxins; D052998:Microcystins; D009153:Mutagens; D010456:Peptides, Cyclic; D013937:Thymidine Kinase; C057862:cyanoginosin LR