Pyrazine-2-carboxylic acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication.

Data source

Reference

Reference Type:

publication

Title:

Poly(adenosinediphosphoribose) Polymerase Inhibitors Stimulate Unscheduled Deoxyribonucleic Acid Synthesis in Normal Human Lymphocytes.

Author:

James L. Sims, Georgina W. Sikorski, Donna M. Catino, Sosamma J. Berger, and Nathan A. Berger

Year:

1982

Bibliographic source:

Biochemistry Vol. 21; Pg. no. 1813-1821, 1982.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

To evaluate the mutagenic potential of 2- Pyrazinecarboxylic acid in Normal human lymphocytes by DNA Repair Synthesis.

GLP compliance:

not specified

Type of assay:

other: DNA Repair Synthesis.

Test material

Test material information

Constituent 1

Reference substance name:

Pyrazine-2-carboxylic acid

EC Number:

202-718-1

EC Name:

Pyrazine-2-carboxylic acid

Cas Number:

98-97-5

Molecular formula:

C5H4N2O2

IUPAC Name:

pyrazine-2-carboxylic acid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Pyrazine-2-carboxylic acid
- Molecular formula (if other than submission substance): C5H4N2O2
- Molecular weight (if other than submission substance): 124.098 g/mol
- Substance type: Organic
- Physical state: Solid

Method

Target gene:

Thymidine

Species / strain

Species / strain / cell type:

lymphocytes: Normal human

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

Not specified

Test concentrations with justification for top dose:

2mM

Vehicle / solvent:

Not specified

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

Human lymphocyte cells not treated with DNA damaging agents are used as a control.

Rationale for test conditions:

Not specified

Evaluation criteria:

The amount of [3H]dTMP incorporated by DNA-damaged cells incubated in the presence of hydroxyurea was taken as the 100% level for unscheduled DNA synthesis.
Stimulation of unscheduled DNA synthesis in the presence of test substance was expressed relative to the 100% level.

Statistics:

Results are presented as the means of assays performed in triplicate.

Results and discussion

Test results

Key result

Species / strain:

lymphocytes: Human

Metabolic activation:

not specified

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

-Other- Pyrazine-2-carboxylic acid showed 0% inhibition of the enzyme, i.e; the compound did not inhibited the enzyme poly(ADP-ribose) polymerase and were unable to stimulate unscheduled DNA synthesis.

Applicant's summary and conclusion

Conclusions:

The test substance 2-Pyrazinecarboxylic acid was unable to stimulate the unscheduled DNA synthesis in UV or MNNG treated human lymphocytes. Thus, the test result was found to be negative.

Executive summary:

DNA repair test was conducted for 2-Pyrazinecarboxylic acid (98 -97 - 5) by using human lymphocytes . It was damaged by treating DNA damaging agents such as UV irradiation or N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). The lymphocytecells were exposed to the test substance pyrazine-2-carboxylic acid for 6 hr incubation with [3H]thymidine in the

presence of 10 mM hydroxyurea.at 37ᵒC.Lymphocyte cells not treated with DNA damaging agents are used as a control. For the DNA repair assay, lymphocyte is prepared in the following manner- Normal human lymphocytes were isolated from peripheral blood and were suspended at 2 × 10⁶cells/mL in complete medium composed of α- modified Eagles medium buffered with 25 mM Hepes, pH 7.2, and supplemented with 10% fetal calf serum, 50 units/mL penicillin, and 50 µg/mL streptomycin.The amount of [³H]dTMP incorporated by DNA-damaged cells incubated in the presence of hydroxyurea was taken as the 100% level for unscheduled DNA synthesis. Stimulation of unscheduled DNA synthesis in the presence of test substance was expressed relative to the 100% level. Results are presented as the means of assays performed in triplicates.96% of DNA synthesis was occurred by the test substance as compared to the control which shows 100% unscheduled DNA synthesis in DNA damaged lymphocytes. The test substance showed 0% inhibition of the enzyme and also were unable to stimulate unscheduled DNA synthesis. Thus, the test was considered to be negative. Therefore 2-Pyrazinecarboxylic acid (98 -97 -5) was not likely to be classified as gene mutant in vitro.