title: Different sensitivities of human colon adenocarcinoma (CaCo-2), astrocytoma (IPDDC-A2) and lymphoblastoid (NCNC) cell lines to microcystin-LR induced reactive oxygen species and DNA damage.
abstract: Microcystins, which are hepatotoxins produced by cyanobacteria, have been reported to be potent tumour promoters, and there is an indication that they can also act as tumour initiators. They thus constitute a potential threat to human and animal health, at concentrations that do not cause acute hepatotoxic effects. The main target organ of microcystin toxicity is the liver; however, several studies have shown that other organs and tissues may also be affected. We have investigated the effect of non-cytotoxic concentrations of microcystin-LR (MCLR) on the generation of intracellular reactive oxygen species (ROS) and on DNA damage in human colon adenocarcinoma CaCo-2, human astrocytoma IPDDC-A2 and human B-lymphoblastoid NCNC cell lines. The viability of CaCo-2 cells exposed to 10 microg/MCLR for 24 and 48 h was reduced by about 40%, while that of NCNC and IPDDC-2A cells was not affected. Intracellular ROS production was increased in CaCo-2 and IPDDC-2A, but not NCNC, cells. Using the comet assay, it was shown that MCLR, at non-cytotoxic concentrations, induced a time and dose dependent increase of DNA damage in CaCo-2 cells, but not significantly in IPDDC-2A and NCNC cells. Thus, CaCo-2 cells were the most sensitive. Their sensitivity is comparable to that observed in our previous study with human hepatoma HepG2 cells. These results indicate that, in addition to liver cells, colon cells should also be considered as a target for microcystin toxicity, and that exposure to low doses of microcystins may affect intestinal tissue.
authors.affiliation: National Institute of Biology, Department for Genetic Toxicology and Cancer Biology, Vecna Pot 111, 1000 Ljubljana, Slovenia. bojana.zegura@nib.si
authors.forename: Bojana
authors.initials: B
authors.lastname: Zegura
authors.forename: Meta
authors.initials: M
authors.lastname: Volcic
authors.forename: Tamara T
authors.initials: TT
authors.lastname: Lah
authors.forename: Metka
authors.initials: M
authors.lastname: Filipic
mesh_terms: D000230:Adenocarcinoma; D001254:Astrocytoma; D001402:B-Lymphocytes; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D008387:Marine Toxins; D052998:Microcystins / Q000494:pharmacology*; D017382:Reactive Oxygen Species
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D017382:Reactive Oxygen Species; C057862:cyanoginosin LR