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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
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:
2007
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
Type of assay:
other: DNA damage response

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
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