Mutagenicity of the mycotoxin patulin in cultured Chinese hamster V79 cells, and its modulation by intracellular glutathione

Schumacher, David M.; Metzler, Manfred; Lehmann, Leane

doi:10.1007/s00204-004-0612-x

Cited by 90 publications

(41 citation statements)

References 30 publications

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“…6) and its precursor 6-methylsalicylic acid are derived from Acetyl-CoA which makes them polyketides and carcinogenic mycotoxins (191,192). They are capable of causing gene mutations in different mammalian cells (193). The administration of patulin subcutaneously twice a week for 15 months showed the development of malignant tumor cells in the area of administration which proved the carcinogenic effect of this mycotoxin.…”

Section: Mycotoxins and Their Carcinogenicitymentioning

confidence: 99%

Effects of different mycotoxins on humans, cell genome and their involvement in cancer

et al. 2017

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Abstract. The chemical nature of most of the mycotoxins makes them highly liposoluble compounds that can be absorbed from the site of exposure such as from the gastrointestinal and respiratory tract to the blood stream where it can be dissimilated throughout the body and reach different organs such as the liver and kidneys. Mycotoxins have a strong tendency and ability to penetrate the human and animal cells and reach the cellular genome where it causes a major mutagenic change in the nucleotide sequence which leads to strong and permanent defects in the genome. This defect will eventually be transcribed, translated and lead to the development of cancer. In this review, the chemical and physical nature of mycotoxins, the action of mycotoxins on the cellular genome and its effect on humans, mycotoxins and their carcinogenicity and mycotoxins research gaps are discussed, and new research areas are suggested. The research review posed various questions. What are the different mycotoxins that can cause cancer, what is the role of mycotoxins in causing cancer and what types of cancers can be caused by mycotoxins? These questions have been selected due to the significant increase in the mycotoxin contamination and the cancer incidence rate in the contemporary world. By revealing and understanding the role of mycotoxins in developing cancer, measures to reduce the risks and incidents of cancer could be taken.

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Section: Mycotoxins and Their Carcinogenicitymentioning

confidence: 99%

Effects of different mycotoxins on humans, cell genome and their involvement in cancer

et al. 2017

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“…In animal studies, patulin has been shown to be toxic, mutagenic, carcinogenic, and teratogenic (Schumacher et al, 2005). Although the mycotoxin has been the subject of several studies, the mechanism of its cellular toxicity remains controversial (Alves et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Patulin influences the expression of Th1/Th2 cytokines by activated peripheral blood mononuclear cells and T cells through depletion of intracellular glutathione

Luft¹,

Oostingh²,

Gruijthuijsen³

et al. 2008

Environmental Toxicology

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Patulin is a mold toxin secreted mainly by fungi of the Penicillium species. Exposure generally results from consumption of moldy fruits and fruit products. Since recent studies identified mold exposure as a risk factor for allergic diseases, we examined the effects of patulin on human peripheral blood mononuclear cells (PBMC) prepared from buffy coats of healthy donors. Cells were stimulated with CD3-and CD28-specific antibodies in the presence or absence of patulin. Effects of patulin on PBMCs were evaluated by proliferation, viability assays, and cytokine ELISAs. The presence of 50 ng/mL patulin strongly decreased the amounts of several cytokines in the supernatant of stimulated PBMCs. This decrease in cytokine secretion was not due to cytotoxic effects of patulin. Moreover, the extent of the reduction of cytokine amounts was cytokine specific, affecting some (IL-4, IL-13, IFNc, and IL-10), but not others . We show that all effects could be abolished by adding thiol containing compounds. A depletion of intracellular GSH could be measured after incubation of cells with patulin. Taken together, our data indicate that patulin modulates the functional activation of PBMCs with respect to proliferation and cytokine secretion patterns by depletion of intracellular GSH. The depletion of intracellular glutathione may influence the balance between Th1 and Th2 cells and have implications for allergic diseases.

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“…V79 cells were cultured in DMEM supplemented with 100 U/ml penicillin, 100 g/ml streptomycin, and 10% FCS, referred to as DMEM complete. The HPRT assay was performed as described previously (18). Briefly, 1.5 ϫ 10 6 V79 cells were seeded in 175-cm 2 cell culture flasks containing 20 ml DMEM complete.…”

Section: Methodsmentioning

confidence: 99%

Quinolone Amides as Antitrypanosomal Lead Compounds with In Vivo Activity

Hiltensperger

Hecht

Kaiser

et al. 2016

Antimicrob Agents Chemother

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e Human African trypanosomiasis (HAT) is a major tropical disease for which few drugs for treatment are available, driving the need for novel active compounds. Recently, morpholino-substituted benzyl amides of the fluoroquinolone-type antibiotics were identified to be compounds highly active against Trypanosoma brucei brucei. Since the lead compound GHQ168 was challenged by poor water solubility in previous trials, the aim of this study was to introduce structural variations to GHQ168 as well as to formulate GHQ168 with the ultimate goal to increase its aqueous solubility while maintaining its in vitro antitrypanosomal activity. The pharmacokinetic parameters of spray-dried GHQ168 and the newly synthesized compounds GHQ242 and GHQ243 in mice were characterized by elimination half-lives ranging from 1.5 to 3.5 h after intraperitoneal administration (4 mice/compound), moderate to strong human serum albumin binding for GHQ168 (80%) and GHQ243 (45%), and very high human serum albumin binding (>99%) for GHQ242. For the lead compound, GHQ168, the apparent clearance was 112 ml/h and the apparent volume of distribution was 14 liters/kg of body weight (BW). Mice infected with T. b. rhodesiense (STIB900) were treated in a stringent study scheme (2 daily applications between days 3 and 6 postinfection). Exposure to spray-dried GHQ168 in contrast to the control treatment resulted in mean survival durations of 17 versus 9 days, respectively, a difference that was statistically significant. Results that were statistically insignificantly different were obtained between the control and the GHQ242 and GHQ243 treatments. Therefore, GHQ168 was further profiled in an early-treatment scheme (2 daily applications at days 1 to 4 postinfection), and the results were compared with those obtained with a control treatment. The result was statistically significant mean survival times exceeding 32 days (end of the observation period) versus 7 days for the GHQ168 and control treatments, respectively. Spray-dried GHQ168 demonstrated exciting antitrypanosomal efficacy.

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Mutagenicity of the mycotoxin patulin in cultured Chinese hamster V79 cells, and its modulation by intracellular glutathione

Cited by 90 publications

References 30 publications

Effects of different mycotoxins on humans, cell genome and their involvement in cancer

Effects of different mycotoxins on humans, cell genome and their involvement in cancer

Patulin influences the expression of Th1/Th2 cytokines by activated peripheral blood mononuclear cells and T cells through depletion of intracellular glutathione

Quinolone Amides as Antitrypanosomal Lead Compounds with In Vivo Activity

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