Mutagenicity of microcystin-LR in human RSa cells.

Suzuki, Hirotsugu; Watanabe, Mariyo F.; Wu, Yanan; Sugita, Takashi; Kita, Kiyoshi; Sato, Takahiro; Wang, X; Tanzawa, H; Sekiya, S; Suzuki, Natsu

doi:10.3892/ijmm.2.1.109

Cited by 15 publications

(13 citation statements)

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“…Whereas the previous studies used diethylnitrosamin as tumor initiator, tumor-promoting activity of MC-LR was also demonstrated in rats after initiation by the natural mycotoxin aflatoxin B 1 [50]. If cyanobacterial extracts are used instead of purified MC, the situation is more realistic and even worse: its genotoxicity has been proven using different test systems, Ames test for mutagenicity using Salmonella typhimurium, or by the detection of ouabainresistant mutation using cultured human RSa cells, comet assay for DNA aberration, and micronucleus test for damage to DNA or mitotic apparatus [51,52]. These findings evidenced the health risk of deprived people, which due to their poverty lack the access to proper food and clean drinking water.…”

Section: Tumor-promoting Capacitymentioning

confidence: 99%

Cyanobacterial toxins – occurrence, biosynthesis and impact on human affairs

Dittmann¹,

Wiegand

2006

Molecular Nutrition Food Res

377

187

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Mass developments of cyanobacteria ("blue-green algae") in lakes and brackish waters have repeatedly led to serious concerns due to their frequent association with toxins. Among these are the widespread hepatotoxins microcystin (MC) and nodularin (NOD). Here, we give an overview about the ecostrategies of the diverse toxin-producing species and about the genes and enzymes that are involved in the biosynthesis of the cyclic peptides. We further summarize current knowledge about toxicological mechanisms of MC and NOD, including protein phosphatase inhibition, oxidative stress and their tumor-promoting capabilities. One biotransformation pathway for MC is described. Mechanisms of cyanobacterial neurotoxins (anatoxin-a, homanatoxin-a, and anatoxin-a(s)) are briefly explained. We highlight selected cases of human fatalities related to the toxins. A special focus is given to evident cases of contamination of food supplements with cyanobacterial toxins, and to the necessary precautions.

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Section: Tumor-promoting Capacitymentioning

confidence: 99%

Cyanobacterial toxins – occurrence, biosynthesis and impact on human affairs

Dittmann¹,

Wiegand

2006

Molecular Nutrition Food Res

377

187

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“…Epidemiological studies have indicated a close relationship between primary liver cancer in human and cynobacteria contaminated drinking water (15,16). While there are several reports showing the in vitro genotoxicity of MCLR (21,22) or cyanobacterial extract (18,19), the evidence for the in vivo genotoxicity of this toxin is less convincing. Therefore, the main objectives of this study were to assess the in vivo genotoxicity of MCLR (if any) and its role in potentiation of DEN induced mutations for its suggested tumor promoting eŠects.…”

Section: Discussionmentioning

confidence: 99%

“…In the same study, however, pure MCLR did not show any mutagenicity in all these strains. MCLR was reported to damage the mitotic spindle apparatus and thus induces polyploidy and apoptosis and necrosis in Chinese hamster ovary (CHO-K1) cells (20), and to induce gene mutation with base substitution in human RSa cells (21). Recently we have demonstrated mutagenic and clastogenic activities of MCLR in human lymphoblastoid cells (TK6) after 24 h treatment in vitro (22).…”

Section: Introductionmentioning

confidence: 99%

Microcystin-LR is not Mutagenic in vivo in the .LAMBDA./lacZ Transgenic Mouse (Muta Mouse)

Honma

Wang

et al. 2006

Genes and Environment

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The water pollution of toxic cyanobacteria (blue-green algae) is causing a serious public health problem in many parts of the world. Microcystin-LR (MCLR) is a potent cyclic heptapeptidic hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. MCLR presents acute and chronic hazards to human health and has been linked to primary liver cancer in humans chronically exposed to this peptide toxin through drinking water. To assess the in vivo mutagenecity of MCLR, the l/lacZ transgenic mice (Muta TM Mouse) were treated with MCLR (1 mg/kg per week x 4) and examined for mutant frequencies (MFs) in the lacZ and cII genes of liver and lungs. Micronucleus induction in peripheral blood cells was also assessed. Co-mutagenic eŠect of MCLR was studied in combination with N-nitrosodiethylamine (DEN). MCLR did not increase either MFs of the target genes in liver and lungs or micronucleus frequency in the peripheral blood cells of the l/lacZ transgenic mouse. While DEN treatment increased MFs signiˆcantly, the co-administration of MCLR did not potentiate its mutagenicity. We conclude that pure MCLR has no in vivo mutagenicity as it failed to induce gene mutation and micronucleus in transgenic mouse. Its tumor promoting eŠect is independent of its interaction to DNA.

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“…Furthermore, it has been suggested that the Adda side chain and possibly the planar ring portion of the peptide are responsible for both recognizing and inhibiting protein phosphatases (73,74 (80,82). In addition, mutations in the K-ras codon 12 in the RSa cell line (83) and DNA fragmentations have been reported after ip injection of cyanobacterial extract or microcystin-LR in mice (84,85). These in vitro and (5,6).…”

Section: Cylindrospermopsinmentioning

confidence: 99%

Cyanobacterial toxins: removal during drinking water treatment, and human risk assessment.

Hitzfeld

Höger

Dietrich

2000

Environ Health Perspect

257

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Cyanobacteria (blue-green algae) produce toxins that may present a hazard for drinking water safety. These toxins (microcystins, nodularins, saxitoxins, anatoxin-a, anatoxin-a(s), cylindrospermopsin) are structurally diverse and their effects range from liver damage, including liver cancer, to neurotoxicity. The occurrence of cyanobacteria and their toxins in water bodies used for the production of drinking water poses a technical challenge for water utility managers. With respect to their removal in water treatment procedures, of the more than 60 microcystin congeners, microcystin-LR (L, L-leucine; R, L-arginine) is the best studied cyanobacterial toxin, whereas information for the other toxins is largely lacking. In response to the growing concern about nonlethal acute and chronic effects of microcystins, the World Health Organization has recently set a new provisional guideline value for microcystin-LR of 1.0 pg/L drinking water. This will lead to further efforts by water suppliers to develop effective treatment procedures to remove these toxins. Of the water treatment procedures discussed in this review, chlorination, possibly micro-/ultrafiltration, but especially ozonation are the most effective in destroying cyanobacteria and in removing microcystins. However, these treatments may not be sufficient during bloom situations or when a high organic load is present, and toxin levels should therefore be monitored during the water treatment process. In order to perform an adequate human risk assessment of microcystin exposure via drinking water, the issue of water treatment byproducts will have to be addressed in the future.

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Mutagenicity of microcystin-LR in human RSa cells.

Cited by 15 publications

References 0 publications

Cyanobacterial toxins – occurrence, biosynthesis and impact on human affairs

Cyanobacterial toxins – occurrence, biosynthesis and impact on human affairs

Microcystin-LR is not Mutagenic in vivo in the .LAMBDA./lacZ Transgenic Mouse (Muta Mouse)

Cyanobacterial toxins: removal during drinking water treatment, and human risk assessment.

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