Statistically designed experiments in a tiered approach to screen mixtures of Fusarium mycotoxins for possible interactions

Tajima, O.; Schoen, Eric D.; Feron, V.J.; Groten, J.P.

doi:10.1016/s0278-6915(01)00124-7

Cited by 72 publications

(51 citation statements)

References 29 publications

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“…In conclusion, this experimental design is suitable for screening purposes, but full factorial assays are necessary to test the specific effects of potential interactive compounds as has also been shown by other authors Tajima et al, 2002). These findings should be validated with other cell lines or preferably with primary cells.…”

Section: Discussionmentioning

confidence: 70%

“…Tested and predicted concentration-response curves were compared to evaluate potential synergistic modes of action. In the third phase, a central composite design was used to screen for possible interactions of all four mycotoxins Groten et al, 1998;Tajima et al, 2002). Toxins indicated to interact with each other in phase three were further tested in a full factorial assay design (phase four) to confirm their interactive effects.…”

Section: Introductionmentioning

confidence: 99%

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In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells

Heussner

Dietrich

O'Brien

2006

Toxicology in Vitro

103

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Hundreds of mycotoxins are known to date and many of them are of great interest with regard to human and animal health since they are detected frequently in plant-derived products. Various mycotoxins may occur simultaneously, depending on the environmental and substrate conditions. Considering this coincident production, it is very likely, that humans and animals are always exposed to mixtures rather than to individual compounds. Therefore, future risk assessments should consider mixture toxicity data. This is particularly true for ochratoxin A (OTA), ochratoxin B (OTB), citrinin (CIT) and occasionally for patulin (PAT) as they are all produced by a number of Penicillium and Aspergillus species. Therefore, these four toxins were chosen to study the interactive effects in vitro, using the well-established porcine renal cell line LLC-PK1 and the MTT reduction test as a cytotoxicity endpoint. By application of a step-wise approach to test combination toxicity, using various full factorial as well as a central composite experimental designs, the interactive (synergistic) cytotoxic effects of the these four toxins were assessed. The results obtained in this study confirm a potential for interactive (synergistic) effects of CIT and OTA and possibly other mycotoxins in cells of renal origin.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells

Heussner

Dietrich

O'Brien

2006

Toxicology in Vitro

103

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“…Other designs that can be used to produce predictive response models and interactive relationships include the central composite design and full factorial designs. One study demonstrated its use in the detection of interactive effects between several mycotoxins commonly found in food or raw materials [19]; this study highlighted the advantage of their tiered central composite design approach to effectively identify two-factor interactions and the utility of full factorial designs for factor validation. Other applications of DoE approaches have been in quantifying synergistic effects of growth factors in stem cell differentiation [20,21].…”

Section: Discussionmentioning

confidence: 96%

Identifying Combinatorial Growth Inhibitory Effects of Various Plant Extracts on Leukemia Cells through Systematic Experimental Design

Cheong¹,

Htay.²,

Tan³

et al. 2012

AJPS

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Plant extracts are widely studied for their anti-cancer and cancer preventive effects. In this study, we compared the leukemia growth inhibition effects of seven different plant extracts, theaflavin, epigallocatechin gallate (EGCG), epicathechin (EC), apigenin, quercetin, chrysin and tannic acid, in vitro using the K562 erythroleukemia cell line and application of the design of experiments (DoE) methodology. Our systematic approach enabled us to isolate the main factor contribution, two-factor interactions and produced interaction relationships and/or models to describe growth inhibitory effects of different plant extracts when they are used in combination. The results identified tannic acid as the most significant inhibitor in this group and had synergistic effects with EGCG at specific concentrations. The fitted model of their combined effects showed that the most potent combination is at low concentrations of tannic acid (10 -20 µM) and high concentrations of EGCG (80 -100 µM). We further showed that tannic acid induced both growth inhibition and apoptosis in K562 cells in ranges between 10 -100 µM. The polyphenol caused cell cycle arrest at G2-phase under the higher concentrations. In summary, use of DoE techniques effectively identified the most prominent inducer in this group of plant bioactive compounds and produced combinatorial bioactivity of various polyphenols and flavonoids over the entire range of concentrations under study. This study exemplifies the usefulness of DoE and serves as a guide in its utility for in vitro assessment of bioactivity in plant constituents.

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“…For some agents, hazards have been identified by epidemiological studies before they were detected in laboratory animals. The contribution of epidemiology to risk assessment has been reviewed in more detail in an earlier FOSIE publication (van den Brandt et al, 2002). However, human epidemiology findings are not always suitable for risk characterisation.…”

Section: 24mentioning

confidence: 99%

“…There is little likelihood that such interactions would occur for the vast majority of man-made chemicals in food because risk characterisation, based on NOAELs and uncertainty factors, aims to ensure that the intake of each individual chemical would be without significant effects. However, in cases where chemicals have the same mode of action on a common target, then concentration addition applies, and effects could be produced, even when the concentrations of each individual chemical is below its no-effect level (Jonker et al, 1996;Tajima et al, 2002), particularly when there may be simultaneous exposure to a large number of chemicals that share a common adverse effect, such as xenoestrogenicity (Rajapakse et al, 2001). Therefore attention needs to be focused during risk characterisation on substances that share a common mode of action.…”

Section: Ways In Which Chemicals May Interactmentioning

confidence: 99%

Risk characterisation of chemicals in food and diet

Renwick

Barlow

Hertz‐Picciotto

et al. 2003

Food and Chemical Toxicology

167

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Statistically designed experiments in a tiered approach to screen mixtures of Fusarium mycotoxins for possible interactions

Cited by 72 publications

References 29 publications

In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells

In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells

Identifying Combinatorial Growth Inhibitory Effects of Various Plant Extracts on Leukemia Cells through Systematic Experimental Design

Risk characterisation of chemicals in food and diet

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