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EC number: 200-001-8 | CAS number: 50-00-0
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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
Data source
Reference
- Reference Type:
- publication
- Title:
- CeIls Deficient in the FANC/BRCA Pathway Are Hypersensitive to Plasma Levels of Formaldehyde
- Author:
- Ridpath, J.R. et al.
- Year:
- 2 007
- Bibliographic source:
- Cancer Res. 67(23): 11117-11122
Materials and methods
- Principles of method if other than guideline:
- Assessment of DNA damage response to plasma levels of formaldehyde in chicken DT40 and colorectal cancer (RKO) cells with targeted mutations in various DNA repair genes.
- GLP compliance:
- not specified
- Remarks:
- This publication do not specify the GLP compliance
- Type of assay:
- other: DNA damage response
Test material
- Reference substance name:
- Formaldehyde
- EC Number:
- 200-001-8
- EC Name:
- Formaldehyde
- Cas Number:
- 50-00-0
- Molecular formula:
- CH2O
- IUPAC Name:
- formaldehyde
- Details on test material:
- - Name of test material (as cited in study report): formaldehyde
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): formaldehyde
- Other: 37% aqueous
Method
Species / strain
- Species / strain / cell type:
- other: Chicken DT40 and colorectal cancer (RKO) cells
- Metabolic activation:
- not specified
- Details on test system and experimental conditions:
- Cell viability was determined by the XTT assay.
Cells were exposed to formaldehyde and allowed to divide for 7 days.
Intracellular GSH was determined using a commercially available kit
Results and discussion
Test results
- Species / strain:
- other: Chicken DT40 and colorectal cancer (RKO) cells
- Additional information on results:
- The DT40-derived mutants showed sensitivity to formaldehyde in the following order: FANCD2>>BRCA2>BRCA1=XRCC2=RAD51C=RAD51D=XRCC3=RAD54>RAD52>parent DT40 cells. No correlation was found between GHS concentrations and formaldehyde-induced cell toxicity, revealing that the homologous recombination pathway rather than the NHEJ pathway is involved in repair of DNA-protein crosslinks (DPC). Nucleotide (NER), base pair excision repair (BER) and some other repair mechanisms were shown to not be involved in DPC repair.
The two most sensitive DT40 mutants (FANCD1 (BRCA2) and FANC2 -deficient cells) show sensitivity to formaldehyde at concentrations between 10-15 µmol/L, which lay below or in the very low range of those of endogenous formaldehyde. Therefore, RKO cells and their isogenic cells disrupted in FANCC or FANCG were exposed to formaldehyde and either FANCC or FANCG were hypersensitive to formaldehyde at concentrations of >20 µmol/L or >38 µmol/L, respectively. Thus cells of human origin showed similar hypersensitivity to formaldehyde. - Remarks on result:
- other: cells of human origin showed similar hypersensitivity to formaldehyde
Any other information on results incl. tables
.
Applicant's summary and conclusion
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