Ames MPF - biotoxik...Ames MPF Xenometrix AG Mutagen Agents • agent (radiation, chemical) which increases the frequency of genetic mutations above the natural background level •

Ames MPF

Dimitrios Spiliotopoulos, PhDXenometrix AG

www.xenometrix.chXenometrix AG

Gewerbestrasse 25CH-4123 Allschwil

http://www.xenometrix.ch/

Ames MPF

Xenometrix AG

Contents

• Mutagen Agents

• Principle of the Assay

– Pre-Incubation Ames Test

– Ames MPF (Ames Multiwell Plate Format)

• Comparing Ames Pre-Incubation Assay Vs. Ames MPF

– Experimental Requirements

– Results

• Ames MPF Kits

• Protocol

• Data Analysis

• Technical Issues

• Conclusions

Summary

Ames MPF

Xenometrix AG

Mutagen Agents

• agent (radiation, chemical) which increases the frequency of genetic mutations above the natural background level

• genotoxic, potentially cytotoxic and likely to be carcinogenic

• can be found everywhere: food, plants, water, soil, chemicals, flame retardants

Mutagens

Ames MPF

Xenometrix AG

• mutagens are tested assessing bacterial reverse mutation using deficiency mutants

– His– S. typhimurium

– Trp– E. coli

• aiming to detect point mutations, i. e.,

– base-pair substitutions (BP)

– frameshift mutation (FS)

• S9 liver fraction mimics mammalian metabolism to consider chemicals’ metabolism

Principle of the Assay[1]

Principle

[1]: PNAS (1972) 69(1):3128–32; PNAS (1973) 70(3):782–6; PNAS (1973) 70(8):2281–5; PNAS (1975) 72(3):979–83

Strains for the Regulatory Ames Plate TestOECD guidelines 471

strain mutation type

TA98TA100TA1537 (or TA97)TA1535TA102

hisD3052hisG46hisC3076G46hisG428

FS BP BP BP BP, [a]

wp2wp2uvrAwp2[pkM101]wp2uvrA[pkM101]

trpE65 [a]

available in Ames MPF kits

[a]: oxidizing agents, crosslinking agents, quinones (e. g., streptonigrin), …

Ames MPF

Xenometrix AG

4-Nitroquinoline-N-oxide

0

10

20

30

40

50

0 0.0625 0.125 0.25 0.5 1

mg/ml

Revetr

an

ts/4

8 w

ells

E-coli Combo

TA98

TA100

TA1535

TA1537

Principle of the AssayWhy so Many Strains?

Principle

Methyl methanesulfonate

0

10

20

30

40

50

0 0.125 0.25 0.5 1

mg/ml

Revetr

an

ts/4

8 w

ells

E-coli Combo

TA98

TA100

TA1535

TA1537

Streptonigrin

0

10

20

30

40

50

0 5 10 20 40

ng/ml

Revetr

an

ts/4

8 w

ells

E.coli Combo

TA98

TA100

TA1535

TA1537

Ames MPF

Xenometrix AG

Principle of the AssayWhy so Many Strains?

Principle

Mitomycin C (without S9)

0

5

10

15

20

25

0 50 100 200 400

ng/ml

Revert

atn

s/4

8 w

ells

uvrA

pKM

Combo

Hydrazine sulfate (without S9)

0

10

20

30

40

50

0 0.25 0.5 1

mg/ml

Revert

an

ts/4

8 w

ells

uvrA

pKM

Combo

Streptonigrin (without S9)

0

10

20

30

40

50

0 6.25 12.5 25 50

ng/ml

Revert

an

ts/4

8 w

ells

uvrA

pKM

Combo

uvrA

pKM

Ames MPF

Xenometrix AG

amino acid–deficient medium


Principle

control sample

auxotrophsHis+




– Trp– E. coli

• point mutations, i. e.,

– base-pair substitutions

– frameshift mutation

• S9 liver fraction mimics mammalian metabolism to make up for the bacterial limited enzyme equipment

Ames MPF

Xenometrix AG



– Trp– E. coli






Principle

auxotrophsprototrophs

control sample

spontaneousreversion

sample–inducedreversion

after two days…

control sample

# ofrevertant

colonies



Ames MPF

Xenometrix AG



– Trp– E. coli






Principle

control sample



after two days…

control sample

# ofrevertant

colonies


Benzo[a]pyreneFound in coal tar, tobacco smoke and many foods (grilled meats).It is not mutagenic,

but its metabolites are.



Ames MPF

Xenometrix AG



– Trp– E. coli






Principle

control sample



after two days…

control sample

# ofrevertant

colonies


sample– S9

sample+ S9

control– S9

control+ S9



Ames MPF

Xenometrix AG

• the Ames assay was moved to a multiwell plate format

– liquid

– low-volume

– colorimetric read-out

• an aminoacid–deficient, bromocresolpurple–containing medium is used as Indicator Medium

– bromocresol purple turns yellow if the pH drops

• metabolically active cells (revertants!)

Multiwell plate format Ames

Ames MPF

10

14

1. no mutagenic activity2. auxotrophs3. bacteria die

1. mutagenic activity2. prototrophs 3. organic acids

10

14

pHpH

Ames MPF

Xenometrix AG

Three Ameses

Three Ames Assay

I. Plate incorporation not defined sample amount due to diffusion!immediate pouring➢ volume not always clearly defined during exposure➢ possible diffusion of sample and cofactors into lower agar

II. Pre–incubation defined sample amount in defined volumeliquid pre-incubation/exposure; dilution with top agar; pouring➢ defined volume during exposure

III. Ames MPF defined sample amount in defined volumeliquid exposure; dilution with indicator medium ➢ defined volume during exposure

minimal glucose agar

I.

pre-incubationmixture

top agar II. III. 24-well exposure plate

384-well plate

Ames MPF

Xenometrix AG

throughput

hands-on time

analysis time

plasticware

needed sample

needed S9

standardization

Comparison

more samples can be tested simultaneously!

241measuring points(per plate)

Pre-IncubationAmes

Ames MPF

automatable[1]

[1]: Mutat Res (2004) 558:181–97

Pre-Incubation Ames Test Vs.Ames MPF

epMotion 5070 automated pipetting system

Ames MPF

Xenometrix AG

throughput

hands-on time

analysis time

plasticware

needed sample

needed S9

standardization

Comparison

1 sample (+ controls), 5 strains (OECD 471), triplicates, +/– S9 mix

Pre-Incub. Ames Ames MPF

ready-to-use agar plates

Concentrations 5 6

Sample dilutions 5 min 5 min

Top agar (tube prep.) 35 min –

Addition sample, culture, S9 50 min 25 min

Plating 40 min –

Transfer to 384-well plates – 40 min

Data analysis 30–100 min c.ca 8 min

Total time c.ca 2 hh c.ca 1 h


Ames MPF

Xenometrix AG




Concentrations 5 6




Plating 40 min –



Total time c.ca 5 hh c.ca 1 ½ h

Comparison


throughput

hands-on time

analysis time

plasticware

needed sample

needed S9

standardization

Ames MPF

Xenometrix AG




Concentrations 5 6




Plating 40 min –



Total time c.ca 5 hh c.ca 1 ½ h

Comparison

error-pronecounting!


throughput

hands-on time

analysis time

plasticware

needed sample

needed S9

standardization

Ames MPF

Xenometrix AG

throughput

hands-on time

analysis time

plasticware

needed sample

needed S9

standardization

Comparison

…and remember the disposal costs!


Ames MPF

Xenometrix AG

throughput

hands-on time

analysis time

plasticware

needed sample

needed S9

standardization

Comparison

5 strains (OECD 471), ½ log dilution steps, triplicates, +/– S9 mix


Top dose 5 mg/plate 5 mg/ml

Compound (mg) 220 55


2 strains, ½ log dilution steps (6 conc.), triplicates, –/+ S9


Top dose:mg/plate mg/ml

5 2 1 5 2 1

Compound (mg) 87.6 35.2 17.6 21.9 8.8 4.4

4–fold reduction of the test item:samples might be limited in quantity

genotoxic impurities

Ames MPF

Xenometrix AG

Comparison

5 strains (OECD 471), ½ log dilution steps, triplicates


S9 fraction (ml)30% 15.57 1.35

10% 5.25 0.45

13–fold reduction of the S9 fraction: reduced number of sacrificed animals

Reuse, Reduce, Recycle


throughput

hands-on time

analysis time

plasticware

needed sample

needed S9

standardization

Ames MPF

Xenometrix AG

throughput

hands-on time

analysis time

plasticware

needed sample

needed S9

standardization

Comparison


database of results for the controls

S9 Certificate of AnalysisQC of the bacterial strains

Ames MPF

Xenometrix AG

Accordance

Accordance with Ames Agar Plate Test

Authors Chemicals Accordance (%)

Notes Explanation forDiscordant Results?

Ref.

Gee et al. 25 88 – –

1998. Mutat Res, 412:115–30.

Gervais et al. 42 company-own 83 –Mainly compounds that specifically revert E.coli and TA1535.

2003.EEMSposter.

Flückiger–Isleret al.

1984.2

(16/19)89.5% inter-lab accordance

–

2004. Mutat Res, 558:181–97.

Flückiger–Isler & Kamber

14 89–100 – –2006.EEMSposter.

Kamber et al. 71 84 –Chemicals requiring reductive metabolism using FMN (hamster liver S9).

2009.Mutagen, 24:359–66.

Flückiger–Isler & Kamber

15 equivocal to weakly positive

87(13/15)

High concordance with the ICH-compliant assay.

–2012. Mutat Res, 747:36–45.

EEMS: European Environmental Mutagen Society

Ames MPF

Xenometrix AG

• a direct comparison of pre-incubation Ames test and Ames MPF assay

same overnight culture(s), chemical, S9-mix preparation

• the methods showed accordance for 13/15 chemicals

some were variable between labs!

confirms the high concordance with the ICH[2]-compliant assay

• higher sensitivity in Ames MPF

+’ve weakly +’ve equivocals –’ve

increase over the baseline > 3-fold 2- < 3-fold ✘b ✘

statistically significant ✓a ✓a ✓ ✘

dose-response ✓a ✓a ✓ ✘

a: statistically significant at least in two adjacent doses or significant increase at the highest non-toxic dose level.b: non or only a single increase without any additional significance.

Weakly Positives and Equivocals[1]

Experimental Setup

[1]: Flückiger–Isler and Kamber, 2012. Mutat Res, 747:36–45[2]: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use

Accordance

Ames MPF

Xenometrix AG

[1]: Flückiger–Isler and Kamber, 2012. Mutat Res, 747:36–45


Comparing the Results

Accordance

Ames MPF

Xenometrix AG


Comparing the Results Correctly

[1]: Flückiger–Isler and Kamber, 2012. Mutat Res, 747:36–45

Accordance

Top dose (mg/ml)

Pre-Incub. MPF

7.1 5.0

Top dose (mg/ml)

Pre-Incub. MPF

5.0 5.0

Ames MPF

Xenometrix AG

“To assess the mutagenic potential of impurities, a single bacterial mutagenicity assay can be carried out with a fully adequate protocol according to ICH S2(R1) and OECD 471 guidelines... For degradants that are not feasible to isolate or synthesize or when compound quantity is limited, … bacterial mutagenicity testing could be carried out using a miniaturized assay format with proven high concordance to the ICH-compliant assay to enable testing at higher concentrations with justification…”


Mutagenic Impurities

Accordance

Ames MPF

Xenometrix AG

• more than 139 chemicals have been tested so far using the Ames MPF assay

• chemicals are constantly tested to improve the assay database

Accordance with Ames Agar Plate TestWork in Progress

Accordance

Ames MPF

Xenometrix AG

Ames MPF samples

• pharmaceuticals

• chemicals

• cosmetics

• pesticides

• drinking water

• waste water

• river sediments

• food-packing material

• electronic cigarette

Ames MPF users

• labs in over 20 countries

• chemical, pharmaceutical and cosmetic industry

• EU and national governmental agencies

• environmental research organizazions

• CRO’s

• biopharma

• military

Ames KitsWhat Can I Use Ames MPF For?

Kits and Uses

Ames MPF

Xenometrix AG

Ames Kits

Ames MPF 98/100Ames II

ScreeningGenotoxic Impurities

Drinking water

Ames MPF 1535, 1537, E. coli Special chemical classes

Ames MPF Penta I• TA98• TA100• TA1535• TA1537• E. coli

ScreeningOECD 471–compliant

Ames MPF 98/100 AQUA waste water analysis

Kits and Uses

Ames MPF

Xenometrix AG

Ames Kits The Kit Content

Kits and Uses

kit name Ames II Ames MPF 98/100Ames MPFPENTA 1

Ames MPFPENTA 2

kit code(s) E10-213A10-210A01-210

C01-512C10-512

B01-513B10-513

strains

Salmonella

TAMix ✓ – – –

TA98 ✓ ✓ ✓ ✓

TA100 – ✓ ✓ ✓

TA1535 – – ✓ ✓

TA1537 – – ✓ ✓

E. coli

uvrA – – ✓ –

pKM101 – – ✓ –

uvrA(pKM101) – – – ✓

positive controls

2–nitrofluorene ✓ ✓ ✓ ✓

2–aminoanthracene ✓ ✓ ✓ ✓

4–nitroquinoline–N–oxide ✓ ✓ ✓ ✓

9–aminoacridine – – ✓ ✓

N4–aminocytidine – – ✓ ✓

2–aminofluorene – – ✓ ✓

growth media

Growth medium ✓ ✓ ✓ ✓

Ampicillin ✓ ✓ ✓ ✓

SalmonellaExposure Medium ✓ ✓ ✓ ✓

Indicator Medium ✓ ✓ ✓ ✓

E. coliExposure Medium – – ✓ ✓

Indicator Medium – – ✓ ✓

metabolic activation

S9 ✓ ✓ ✓ ✓

Ames MPF

Xenometrix AG

Ames Kits The Kit Content

Kits and Uses

Individual Xenometrix Ames MPF products can also be purchased.

Ames MPF

Xenometrix AG

Ames KitsA Few Points

• all products are QC’ed after production

• kit products can be individually purchased and

S9 cofactor kit (PCO-0800) is separately available

• while we warmly recommend to perform measurements in as many strains as possible in triplicate, other experimental designs (unicates, duplicates) are also possible for screening purposes

• support for data analysis

Kits and Uses

Ames MPF

Xenometrix AG

Quality Control performed for each bacterial lot includes, but is not limited to, the assessment of the following criteria

• presence of pKM101 plasmid

• defective DNA repair

• defective lipopolysaccharide cell wall

• bacterial cellular morphology and aggregation

• absence of bacterial contamination

• dose–response behavior for positive controls

Ames Kits QC and CoA

Kits and Uses

S9 Certificate of Analysis

Ames MPF

Xenometrix AG

Ames Kits Do I Have Everything I Will Need?

• Environmental shaker capable of 37°C, 250 rpm incubations with approx. 2.5 - 3 cm amplitude. For shakers with smaller amplitude, alternative incubation vessels and rotational speeds can be used

• 37°C dry incubator • Spectrophotometer to measure the optical density at 600 nm • 20 μl, 200 μl, and 1000 μl adjustable pipettes and sterile tips • 5-50 μl and 50-200 μl 8-channel pipettes • 8-channel repeating pipettor and sterile tips (highly recommended) • Light table for scoring results (recommended)

• 50 ml tubes with (filter) caps • 24-well plates • 384-well microtiter plates • 96-well microtiter plate • Reagent reservoirs • 5 ml and 10 ml pipettes • Spectrophotometer cuvettes • Solvents for sample dilution and solvent control • S9 buffer components*

*A ready-to-use kit available separately from Xenometrix containing phosphate buffer pH 7.4, MgCl2, KCl, G-6-P and NADP for preparing the S9 mix S9 Cofactor kit (Art. No. PCO-0800). This kit replaces the self-made S9 buffer components (for which the composition is provided in the Instructions for Use).

All plasticware must be sterile!

Kits and Uses

Ames MPF

Xenometrix AG

ProtocolDay 0

Protocol

1. prepare 10 ml only of medium and, if necessary (TA98, TA100 and pKM101), Ampicillin

2. thaw the bacterial stock:

- semisolid: disrupt the pellet in 200 µl and inoculate 25 µl

- liquid: inoculate 10 µl

3. make sure the bacteria will have enough air for the night

4. grow at 37°C for 14–16 hours shaking at 250 rpm (if using a 50-ml tube)

Prepare

Growth Medium

12

Bacterial

stock

grow at 37°C

for 12 – 15 hours

shaking at 250 rpm

4

Loose cap

3

Ames MPF

Xenometrix AG

Prepare sample

dilutions in

mw24 plates

2

ProtocolDay 1 – part 1/2

Protocol

1. check bacterial OD600 values

2. prepare sample and control dilutions

3. dilute bacterial culture in the Exposure Medium

- if needed, prepare S9 mix

4. expose the bacteria to the prepared samples

5. incubate at 37°C at 250 rpm

C–

C+

D6

D5

D4

D3

D2

D1

C–

C+

D6

D5

D4

D3

D2

D1

C–

C+

D6

D5

D4

D3

D2

D1

repl. #1 #2 #3

Dilute bacteria in

the Exposure

Medium

3

Incubate at 37°C

at 250 rpm5

Expose the bacteria

To the samples4

Ames MPF

Xenometrix AG

ProtocolDay 1 – part 2/2

Protocol

1. add Reversion Indicator Medium

2. transfer to 384-well plates

6 (=3×2) 384-well plates per sample dilution if testing with and without S9 (instead of 48 agar plates)

3. incubate at 37°C for two days

Add Reversion

Indicator Medium1

C–

C+

D6

D5

D4

D3

D2

D1

C–

C+

D6

D5

D4

D3

D2

D1

Transfer to 384-well

plate2

Incubate at 37°C

for two days.

3

Ames MPF

Xenometrix AG

ProtocolDay 3

Protocol

1. count the yellow wells and analyze the results.

Note: for the analysis of your data Xenometrix suggests to use a threshold based on the solvent control results of the experiment, namely the baseline, defined as the average of the solvent control’s positive wells plus one standard deviation.

C–

D1

D2

D3

D4

D5

D6

C+

Ames MPF

Xenometrix AG

Data Analysis

• Excel worksheets are provided for the analysis of the data generated with Ames II and Ames MPF and with Ames Penta (shown in the next slides)

• as per the generally accepted criteria, results are considered significant when

– 2-fold higher than the baseline:

• the baseline is defined as the sum of average and 1 standard deviation of the solvent control

– dose dependence:

• “A positive result in a spot test is generally not considered to be adequate evidence for mutagenicity. Mutagenicity should be confirmed by demonstrating a dose–response relationship…” Mutat Res (1985) 113:173–215

“Statistical methods may be used as an aid in evaluating the test results (…). However, statistical significance should not be the only determining factor for a positive response.” OECD 471

Data Analysis

Ames MPF

Xenometrix AG

Data Analysis – Penta“Concentrations” Worksheet

Data Analysis

Ames MPF

Xenometrix AG

Data Analysis – Penta“raw data” Worksheet

Data Analysis

Ames MPF

Xenometrix AG

Data Analysis – Penta“Summary” Worksheet

Data Analysis

Ames MPF

Xenometrix AG

Data Analysis – Penta “Graphs” Worksheet

Data Analysis

Ames MPF

Xenometrix AG

Technical IssuesGeneral Recommendations

• immediately store bacteria at –80°C and keep them at –80°C until use

do not re-freeze bacteria for later use: their growth and performance may be compromised!!

• the bacteria must have grown sufficiently well OD600 > 2.0 (with OD600 neg. control <0.05)

• solvents:

– DMSO is fine;

– if using volatile compounds and/or solvents, pipette fast the test item from the mw96 plate to the mw24 plate

• do not mix Salmonella and E. coli media: they have different compositions!

Technical (1/5)

Ames MPF

Xenometrix AG

• some strain intrinsically have higherspontaneous reversion rates

• for each lot of the bacterial strainsthe internal Quality Controlminimizes the chances of observinga high spontaneous reversion rate

• high rates of spontaneous reversiongenerally occur due to mishandlingduring the shipment

• the Instructions for Use provide a protocol to address this issueselecting a 2-day, cost-effectivesubculture pre-selection

• alternatively, new vials (new lots) can be shipped

Technical IssuesHigh Spontaneous Revertants

Technical (2/5)

Ames MPF

Xenometrix AG

Technical Issues48-Well Limit: Is It a Limit?

Technical (3/5)

In the presence of strong mutagens, the increase of revertants is…

● potentially unlimited in the Ames agar test

● plateauing at 48-well in the Ames MPF

but in the Ames MPF…

➢ repeated 48-well revertant counts confirm the results for strong mutagens

➢ lower number of spontaneous revertants

➢ higher sensitivity (detection of lowest mutagenic concentration)

strong mutagen

Ames MPF

Xenometrix AG

Technical Issues48-Well Limit: Solvent Control

Technical (3/5)

15–30 100–200

40–70

Values referto the

agar plateAmes tests

Ames MPF

Xenometrix AG

Technical Issues48-Well Limit: Is It a Limit?

Technical (3/5)

strong mutagen weak mutagen

In the presence of strong mutagens, the increase of revertants is…

● potentially unlimited in the Ames agar test

● plateauing at 48-well in the Ames MPF

but in the Ames MPF…

➢ repeated 48-well revertant counts confirm the results for strong mutagens

➢ lower number of spontaneous revertants

➢ higher sensitivity (detection of lowest mutagenic concentration)

Ames MPF

Xenometrix AG

Fold Increase Over the Baseline

Technical Issues48-Well Limit: Is It a Limit? No.

Technical (3/5)

• Low spontaneous revertants → larger dynamic range

• Selection of cultures with low spontaneous revertant rate at Xenometrix with two Quality Controls

• The baseline adapts to the culture whether it is high spontaneous revertants (•) or low spontaneous revertants (•)

• Pass/Fail criteria for spontaneous revertants in Ames MPF

Number of Positive Wells

Ames MPF

Xenometrix AG

Fold Increase Over the Baseline

Technical Issues48-Well Limit: Is It a Limit? No.

Technical (3/5)

• Low spontaneous revertants → larger dynamic range

• Selection of cultures with low spontaneous revertant rate at Xenometrix with two Quality Controls

• The baseline adapts to the culture whether it is high spontaneous revertants (•) or low spontaneous revertants (•)

• Pass/Fail criteria for spontaneous revertants in Ames MPF

Number of Positive Wells

Ames MPF

Xenometrix AG

Technical IssuesCytotoxicity

Technical (4/5)

If cytotoxicity occurs, the dose range must be adjusted!

Note: this also applies to the agar plate Ames tests!

How can I detect cytotoxicity?

1. Dose-dependent reduction of revertant wells

With Ames MPF additional indications suggest cytotoxicity!

2. Increased brilliance of purple medium

3. Lipid droplets (bubbles) in the absence of S9

[sample]

revertants’number

mutagenicity

cytotoxicity

Ames MPF

Xenometrix AG


Technical (4/5)








Ames MPF

Xenometrix AG


Technical (4/5)








Ames MPF

Xenometrix AG

Technical IssuesColored Compounds

Technical (5/5)

2.05

s.c.

5.1

12.8

80

32

200

p.c.

µg/ml

orange sample

Ames MPF

Xenometrix AG

Ames MPF AssaysAccolades

Conclusions

Chapter 5Perspectives in genotoxicity screening“Ames II (Xenometrix, Switzerland) is a microplate-based fluctuation test version of the Ames test and probably the best Ames predictor.”

Chapter 9Mutation Research

New Paradigms for the Environmental Assessment, p. 26“Thus, the all-liquid format of the Ames II/MPF assay, which requires less test compound and allows for the use of multichannel pipettes, thus automating the pipetting steps, makes this procedure an attractive method to evaluate mutagenicity of a large number of samples at the same time - a common situation in environmental monitoring”.

… it has been proposed by the European Union-fundedREBECA project as a screening tool to determine whether

fungal biological control agents produce genotoxic/mutagenic metabolites which require further

attention in the regulatory risk assessment.

Chapter 2: The Ames II and Ames MPF Penta I Assay: A Liquid Microplate Format Modification of the Classic Ames Test

Chapter 10: Ames II and Ames Liquid Format

Mutagenicity Screening Assays

Ames MPF

Xenometrix AG

Advantages

• 4× less test sample necessary

• liquid microplate format allows for

– less hands-on time

– simultaneous processing of several replicates

– higher throughput

– potentially partial automation

• 12× less consumption of S9 – 3Rs[1]

• quick, easy, less error–prone colorimetric read-out

• less plasticware, less contaminated waste in environment

• listed explicitly in ICH M7 Guideline

• (depending on compound) higher sensitivity[1]: Replace, Reduce, Refine

Disadvantages

• not listed explicitly in OECD 471

• not same large database as agar plate method

Ames MPF AssaysConclusions

Conclusions

Ames MPF

Xenometrix AG

Questions?

Questions?

Ames MPF

Xenometrix AG

Contacts

Nicole Weiland, PhD CEOBusiness Development

[email protected]

Nicolas Nicaise Technical Support

[email protected]

Dimitrios Spiliotopoulos, PhDDevelopment and Production

[email protected]

Contacts

mailto:[email protected]



Ames MPF

Dimitrios Spiliotopoulos, PhDXenometrix AG

www.xenometrix.chXenometrix AG

Gewerbestrasse 25CH-4123 Allschwil

http://www.xenometrix.ch/

Documents

Ames MPF - biotoxik...Ames MPF Xenometrix AG Mutagen Agents • agent (radiation, chemical) which increases the frequency of genetic mutations above the natural background level •