CYN is toxic to liver and kidney tissue and is thought to inhibit protein synthesis and to covalently modify DNA and/or RNA.
The outbreak was traced back to a bloom of Cylindrospermopsis raciborskii in the local drinking water supply, and the toxin was subsequently identified.
C. raciborskii has been observed mainly in tropical areas, however has also recently been discovered in temperate regions of Australia, North, South America, New Zealand and Europe.
Urine analysis revealed high levels of proteins, ketones and sugar in many patients, along with blood and urobilinogen in lesser numbers.
Initial thoughts on the cause included poor water quality and diet, however none were conclusive, and the illness was coined the “Palm Island Mystery Disease”.
[4] At the time, it was noticed that this outbreak coincided with a severe algal bloom in the local drinking water supply, and soon after the focus turned to the dam in question.
[5] A study of the dam revealed that periodic blooms of algae were caused predominantly by three strains of cyanobacteria: two of the genus Anabaena, and Cylindrospermopsis raciborskii, previously unknown in Australian waters.
[9] Isolation of the toxin using cyanobacteria cultured from the original Palm Island strain was achieved by gel filtration of an aqueous extract, followed by reverse-phase HPLC.
Sensitivity of key signals in the NMR spectrum to small changes in pH suggested that the uracil ring exists in a keto/enol tautomeric relationship, where a hydrogen transfer results in two distinct structures (Figure 2).
[8] A second metabolite of C. raciborskii was identified from extracts of the cyanobacteria after the observation of a frequently occurring peak accompanying that of CYN during UV and MS experiments.
Analysis by MS and NMR methods concluded that this new compound was missing the oxygen adjacent to the uracil ring, and was named deoxycylindrospermopsin (Figure 3).
[16] Hawkins et al.. demonstrated the toxic effects of CYN by mouse bioassay, using an extract of the original Palm Island strain.
Froscio et al.. proposed that CYN has at least two separate modes of action: the previously reported protein synthesis inhibition, and an as-yet unclear method of causing cell death.
[22] Shaw et al.. demonstrated that the toxin could be metabolised in vivo, resulting in bound metabolites in the liver tissue, and that damage was more prevalent in rat hepatocytes than other cell types.
[26] Humpage et al. also supported this, and in addition postulated that CYN (or a metabolite) acts on either the spindle or centromeres during cell division, inducing loss of whole chromosomes.
Of these the latter, which produces CYN, has attracted considerable attention, not only due to the Palm Island outbreak, but also as the species is spreading to more temperate areas.
Previously, the algae was classed as only tropical, however it has recently been discovered in temperate regions of Australia, Europe,[3] North and South America,[6] and also New Zealand.
Analysis revealed that the water contained both extracellular and intracellular CYN, and that the crayfish had accumulated this primarily in the liver but also in the muscle tissue.
Moreover, 2000 site-days of recreation were also lost, and the economic cost was estimated at A$10 million, after taking into account indirectly affected industries such as tourism, accommodation and transport.
[38] Current methods include liquid chromatography coupled to mass spectrometry (LC-MS),[39][40] mouse bioassay,[41] protein synthesis inhibition assay, and reverse-phase HPLC-PDA (Photo Diode Array) analysis.