4-hydroxy-3-methoxycinnamic acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

publication

Title:

Modifying effects of components of plant essence on the induction of sisterchromatid exchanges in cultured Chinese hamster ovary cells

Author:

Sasaki et al

Year:

1989

Bibliographic source:

Mutation Research, 226 (1989) 103-110

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study was designed to investigate the influence of 21 kinds of components of plant essence including ferulic acid on spontaneous as well as on mitomycin C, UV- and X-ray-induced SCEs.

GLP compliance:

no

Type of assay:

sister chromatid exchange assay in mammalian cells

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxy-3-methoxycinnamic acid

EC Number:

214-490-0

EC Name:

4-hydroxy-3-methoxycinnamic acid

Cas Number:

1135-24-6

Molecular formula:

C10H10O4

IUPAC Name:

4-hydroxy-3-methoxycinnamic acid

Test material form:

solid

Specific details on test material used for the study:

The components of plant essence tested were as follows: anethol, benzaldehyde, caffeic acid, DLcamphene, caryophyllene, cineole, citronellal, cuminal aldehyde, ellagic acid, eugenol, ferulic acid, geraniol, isoeugenol, jasmone, d-(+)- limonene, linallol, I-phellandrene, alpha-pinene, pulegonol, scopoletin and timole. Eight analogues of caffeic acid and ferulic acid investigated were 3-phenyl propylaldehyde, cinnamyl alcohol, cinnamyl acetate, cinnamic acid, cinnamide, methyl cinnamate, ethyl cinnamate, and vinyl cinnamate.

Ferulic acid:
Ferulic acid was purchased from Tokyo Kasei Kogyo, Tokyo.
Ferulic acid was dissolved in dimethyl sulfoxide (DMSO). The final concentration of DMSO in the medium was 0.5 %

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

Cells and media:
Chinese hamster K-I (CHO K-l) cells were obtained from the American Type Culture Collection, cloned in our laboratory and grown in Ham's F12 medium in a humidified atmosphere with 5% CO2 at 37°C. The medium was supplemented with 10% fetal bovine serum, 50 IU/ml penicillin G, 50 µg/ml streptomycin sulfate and 2.5 µg/ml fungizon. Medium and all antibiotics were obtained from Flow Laboratories, Inc. (U.S.A.).

Metabolic activation:

without

Test concentrations with justification for top dose:

0, 1.0, 3.3, 10, 33.3, 100 μM Corresponding to 0, 0.641, 1.94, 6.41, 19.4, 64.1 μg/ml (Calculated based on molecular weight = 194.19.)

Vehicle / solvent:

- Vehicle used: Ferulic acid was dissolved in dimethyl sulfoxide (DMSO). The final concentration of DMSO in the medium was 0.5 %

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Results:
- The ferulic acid did not influence cell cycle (data not shown) and spontaneous SCEs at the concentrations used (0, 0.641, 1.94, 6.41, 19.4, 164.1 μg/ml)
- Post-treatment of mitomycin C treated cells with the ferulic acid increased the frequency of induced SCEs in a dose-related manner. The effect was statistically significant (p<0.001) at the two highest non toxic concentrations ( 33.3 and 100 μM).
- The frequency of SCEs induced by UV was significantly increased by treatment with ferulic acid at 10 (0.001

Additionnal results:
These results suggest that an alpha beta-unsaturated carbonyl group may be necessary for the SCE- enhancing effect.
The frequency of X ray- induced SCEs was decreased when cells in the G1 phase were treated with caffeic acid or ferulic acid. The frequency of UV-induced SCEs was, however, increased when cells in the S phase were treated with these compounds.

Remarks on result:

other:

Remarks:

spontaneous SCEs at the concentrations used.

Applicant's summary and conclusion

Conclusions:

The ferulic acid did not influence cell cycle (data not shown) and spontaneous SCEs at the concentrations used i.e. 0, 0.641, 1.94, 6.41, 19.4, 64.1 μg/ml

Executive summary:

This study was designed to investigate the influence of 21 kinds of components of plant essence including ferulic acid on spontaneous as well as on mitomycin C, UV- and X-ray-induced SCEs.

As results:

- The ferulic acid did not influence cell cycle (data not shown) and spontaneous SCEs at the concentrations used (0, 0.641, 1.94, 6.41, 19.4, 64.1 μg/ml)

- Post-treatment of mitomycin C treated cells with the ferulic acid significantly increased the frequency of induced SCEs in a dose-related manner.

Further investigation of the SCE-enhancing effect of analogues of caffeic acid and ferulic acid revealed that an alpha beta -unsaturated carbonyl group

may be necessary for SCE-enhancing effects.

-The influence of ferulic acid on X-ray- or UV-induced SCEs was also studied. The frequencies of SCEs induced by UV were increased by treatment with this compound. This increasing effect was observed in the S phase of the cell cycle. On the contrary, X-ray-induced SCEs were reduced by the treatment with this compound. The decreasing effect was observed in the G1 phase but not in the S or G2 phase. To explain these contradictory results, the authors assumed that ferulic acid may modify the repair of DNA strand breaks.