Preliminary evidence for in vivo tumour initiation by oral administration of extracts of the blue-green alga Cylindrospermopsis raciborskii containing the toxin cylindrospermopsin

New reports indicate that the toxic alkaloid cylindrospermopsin occurs in cyanobacteria in Israel, Florida, South America, and Australia in drinking water sources. This toxin is now recognised as a potential threat to human health. Furthermore, we have recently demonstrated the mutagenicity of cylindrospermopsin in vitro in a human lymphoblastoid cell-line. Therefore it is essential to determine whether cylindrospermopsin is also carcinogenic in vivo. In this preliminary study, 53 mice were treated up to three times orally with Cylindrospermopsis raciborskii extract containing cylindrospermopsin, while 27 control mice were treated with saline. A proportion of each group were then given O-tetrade-canoylphorbol 13-acetate (10 mug/mouse, twice weekly in liquid food) for the duration of the experiment; the remainder were given a control diet. After 30 weeks, the mice were euthanased and the major organs were examined histologically. Five tumours were found in 53 cylindrospermopsin-treated mice while none were found in the 27 controls. Although the number of animals used was too low to provide statistical significance (p = 0.16), the calculated relative risk (RR = 6.2; 95% CI: 0.33-117) indicates a potential biological and public health significance requiring further investigation. Estimates are given of the size of experiment required to provide statistical proof of cylindrospermopsin carcinogenicity. (C) 2001 by John Wiley & Sons, Inc.