Unique features of the okadaic acid activity class of tumor promoters

Fujiki, Hirota; Suganuma, Masami

doi:10.1007/s004320050257

Cited by 93 publications

(57 citation statements)

References 14 publications

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“…Among more than 60 types of MCs identified, MC-RR and LR were the dominant types of MCs worldwide (Haider et al, 2003), which have been found from fresh water bodies to oceans and shown tumor promoting activity through the inhibition of protein phosphatases (Fujiki and Suganuma, 1999). Recently, a provisional safety guideline of 1.0 lg l À1 MC-LR in drinking water was recommended by WHO (Falconer, 1999).…”

Section: Introductionmentioning

confidence: 99%

Adsorption of microcystins by carbon nanotubes

et al. 2006

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The production of cyanobacterial toxins microcystins (MCs) by cyanobacterial bloom which may promote the growth of tumor in human liver is a growing environmental problem worldwide. In this paper, the adsorption of MC-RR and LR, which were extracted from cyanobacterial cells in Dianchi Lake in China, by carbon nanotubes (CNTs), wood-based activated carbon (ACs) and clays were investigated. Compared with ACs and clay materials of sepiolite, kaolinite and talc tested, CNTs were found to have a strong ability in the adsorption of MCs. At the concentrations of 21.5 mg l À1 MC-RR and 9.6 mg l À1 MC-LR in 50 mmol phosphate buffer solution (pH 7.0), the adsorption amounts of MCs by CNTs with the range of outside diameter from 2 to 10 nm were 14.8 and 5.9 mg g À1 , which were about four times higher than those by other adsorbents tested. It was shown that with the decrease of CNTs outside diameters from 60 to 2 nm, the adsorption amount of MCs was apparently increased, however the size of CNTs particles formed in solution declined. This result implies that the size of CNTs tube pore that is fit for the molecular dimension of MCs plays a dominant role. Furthermore the specific surface area of CNTs was also found to be a factor in the adsorption of MCs. The results suggested that the selection of suitable size of CNTs as a kind of adsorbent is very important in the efficient eliminating MCs from drinking water in future.

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Section: Introductionmentioning

confidence: 99%

Adsorption of microcystins by carbon nanotubes

et al. 2006

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“…18 The algal toxin okadaic acid (OA) is a potent inhibitor of a subgroup of serine/threonine phosphatases, including the two most abundant phosphatases, PP1 and PP2A, in mammalian cells. 19 ± 21 Although prolonged exposure to low concentrations of OA promotes tumour formation, 22 acute exposure of cells to moderate or high concentrations of OA invariably leads to apoptosis. 23 ± 28 OA-induced death can be both dependent and independent of gene transcription, protein synthesis, p53 expression, and caspases.…”

Section: Introductionmentioning

confidence: 99%

Establishment of okadaic acid resistant cell clones using a cDNA expression library

2001

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The mechanism whereby the universal apoptogen and serine/ threonine phosphatase inhibitor okadaic acid (OA) kills cells, is still unclear. To create a novel tool for probing of OA action, fibroblasts were selectedfor OA-resistance after infection with a retroviral Jurkat T-cell cDNA expression library. Twenty-one cloneswereselected. Twoof these(OAR1,OAR2)werestudied in detail. OAR1 and 2 had each a retrovirally introduced short cDNA, corresponding to a human gene (oar1 and oar2, respectively) with unknown function. Reintroduction of oar1 or oar2 cDNA into wild-type cells reproduced the OA-resistant phenotype. OAR1 and 2 were cross-resistant to other phosphatase inhibitors (calyculin A, cantharidin), but not to staurosporineor microinjectedCytochromec,thus,indicating a disturbance in a limited number of death pathways, upstream or independent of apaf-1/caspases-3/9. The action of OA involved caspase-dependent and caspase-independent components. Both components were less efficient in OAR1 and 2, than in wild-type cells. Subtle differences existed between OAinduced phosphoprotein patterns in wild-type cells, OAR1, and OAR2, indicating that a narrow selection of protein phosphorylation events had been targeted. We propose that the clones have defects in a hitherto non-elucidated signal pathway linking OA-induced protein phosphorylation to initiation of a death execution pathway provided with a caspase-dependent amplification loop. The novel OAresistant cell clones will be used to elucidate the significance for apoptosis of oar1 and 2, their link to altered protein phosphorylation, and the potential link of the latter to initiation of apoptosis. Cell Death and Differentiation (2001) 8, 754 ± 766.

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“…Acute intoxications with microcystins result in fulminant liver damage (Runnegar and Falconer 1982). Microcystins and nodularins have also been shown to be tumor promoters (Fujiki and Suganuma 1999).…”

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confidence: 99%

Effect of ozonation on the removal of cyanobacterial toxins during drinking water treatment.

Hoeger

Dietrich

Hitzfeld

2002

Environ Health Perspect

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Water treatment plants faced with toxic cyanobacteria have to be able to remove cyanotoxins from raw water. In this study we investigated the efficacy of ozonation coupled with various filtration steps under different cyanobacterial bloom conditions. Cyanobacteria were ozonated in a laboratory-scale batch reactor modeled on a system used by a modern waterworks, with subsequent activated carbon and sand filtration steps. The presence of cyanobacterial toxins (microcystins) was determined using the protein phosphatase inhibition assay. We found that ozone concentrations of at least 1.5 mg/L were required to provide enough oxidation potential to destroy the toxin present in 5 X 10(5 )Microcystis aeruginosa cells/mL [total organic carbon (TOC), 1.56 mg/L]. High raw water TOC was shown to reduce the efficiency of free toxin oxidation and destruction. In addition, ozonation of raw waters containing high cyanobacteria cell densities will result in cell lysis and liberation of intracellular toxins. Thus, we emphasize that only regular and simultaneous monitoring of TOC/dissolved organic carbon and cyanobacterial cell densities, in conjunction with online residual O(3) concentration determination and efficient filtration steps, can ensure the provision of safe drinking water from surface waters contaminated with toxic cyanobacterial blooms.

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Unique features of the okadaic acid activity class of tumor promoters

Cited by 93 publications

References 14 publications

Adsorption of microcystins by carbon nanotubes

Adsorption of microcystins by carbon nanotubes

Establishment of okadaic acid resistant cell clones using a cDNA expression library

Effect of ozonation on the removal of cyanobacterial toxins during drinking water treatment.

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