Micronucleus induction and chromosome loss in transformed human white cells indicate clastogenic and aneugenic action of the cyanobacterial toxin, cylindrospermopsin

Cylindrospermopsin (CYN) is a potent inhibitor of protein synthesis produce d by a number of cyanobacterial species, the most common being Cylindrosper mopsis raciborskii. CYN contains a uracil moiety attached to a sulphated gu anidino moiety, suggesting that it may have carcinogenic activity. This rep ort describes the use of the WIL2-NS lymphoblastoid cell-line in the well-v alidated cytokinesis-block micronucleus (CBMN) assay to test this hypothesi s. Centromeres (CENs) were identified in micronuclei (MNi) of binucleated c ells (BNCs) by fluorescent in situ hybridisation of alpha centromeric DNA s equence repeats. The results indicate that CYN induced a significant increa se in the frequency of MNi in BNCs exposed to 6 and 10 mug/ml. and a signif icant increase in CEN-positive MNi at all concentrations of CYN tested (1, 3, 6, and 10 mug/ml). However. despite this apparently greater sensitivity of WIL2-NS cells to induction of CEN-positive MNi at low CYN concentrations , at the higher concentrations the magnitude of the increase in CEN-positiv e MNi did not account for the greater increase in MNi in BNCs, indicating t hat both CEN-positive and CEN-negative MNi were induced. This suggests that CYN acts to induce cytogenetic damage via two mechanisms, one at the level of the DNA to induce strand breaks, the other at the level of kinetochore/ spindle function to induce loss of whole chromosomes (aneuploidy). C. racib orskii occurs in a number of human drinking water sources worldwide and so these findings may have important public health implications. (C) 2000 Publ ished by Elsevier Science B.V.