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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro DNA damage and/or repair study
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comet assay not performed using GLP.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2007

Materials and methods

Principles of method if other than guideline:
A single cell gel/comet assay in mammalian cells for detection of DNA damage was performed.
GLP compliance:
no
Type of assay:
comet assay

Test material

Constituent 1
Details on test material:
- Purity: highest purity available

Method

Target gene:
SV-40 immortalized human uroepithelial cell lines (SV-HUC-1)
Species / strain
Species / strain / cell type:
mammalian cell line, other: SV-40 human uroepithelial cell lines (SV-HUC-1)
Details on mammalian cell type (if applicable):
- Cell line obtained from American Type Culture Collection (ATCC, Wiltshire, USA)
- The mouse monoclonal primary antibody used was p53 PAb240 (NCL-p-53-240) from Novocastra (Newcastle, UK). The rabbit polyclonal antibody COX-2 (CP222C) was from BioCare Medical (Concord, Canada).
Metabolic activation:
not applicable
Test concentrations with justification for top dose:
0, 2, 5, 10, 20, and 40 µg/mL

Results and discussion

Test results
Species / strain:
mammalian cell line, other: SV-40 human uroepithelial cell line SV-HUC-1
Metabolic activation:
not applicable
Genotoxicity:
positive
Remarks:
as increased density of mutant p53 and COX-2 protein expression
Cytotoxicity / choice of top concentrations:
cytotoxicity

Any other information on results incl. tables

Test substance treatment reduced cell viability in a dose-dependant manner. The test substance caused DNA damage on SV-HUC-1 cells. The report shows the expression level of mutant p53 and COX-2 analysis by immunocytochemistry analysis after treatment with the test substance in SV-HUC-1 cell lines. Test substance treatment increased mutant p53 and COX-2 proteins expression.

Applicant's summary and conclusion

Conclusions:
Under the conditions employed in this study, test substance exposure resulted in cytotoxicity in the SV-40 human uroepithelial cell line and increased expression of mutant p53 and COX-2 proteins.
Executive summary:

A single cell gel/comet assay in mammalian cells for detection of DNA damage was performed. Test substance treatment reduced cell viability in a dose-dependant manner. The test substance caused DNA damage on SV-HUC-1 cells. The report shows the expression level of mutant p53 and COX-2 analysis by immunocytochemistry analysis after treatment with the test substance in SV-HUC-1 cell lines. Test substance treatment increased mutant p53 and COX-2 proteins expression. Under the conditions employed in this study, test substance exposure resulted in cytotoxicity in the SV-40 human uroepithelial cell line and increased expression of mutant p53 and COX-2 proteins.