Registration Dossier

Toxicological information

Specific investigations: other studies

Currently viewing:

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Very well documented paper on bisulfite-induced changes in protein expression in Syrian hamster foetal cells.

Data source

Reference
Reference Type:
publication
Title:
Altered polypeptide expression associated with neoplastic transformation of Syrian hamster cells by bisulfite.
Author:
Wirth, P.J. et al.
Year:
1986
Bibliographic source:
Cancer Research 46, 390-339

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Proteomic analysis of changed polypeptide expression in Syrian hamster foetal cells (HFC). Cells from a secondary culture were exposed 24 h after plating for 15 min to 20 mM sodium bisulfite in PBS (0, 1, 5, 10, or 20 mM). After being incubated for a total of 7 days, morphologically transformed colonies were ring isolated and expanded. Within 6 weeks cell populations were injected subcutaneously into nu/nu mice to determine tumorigenicity. Cell lines of proven malignancy but which had not been derived from tumours were used exclusively. Amino acid-labelled [14C]-polypeptides from neoplastic and non-transformed parental foetal cells were separated by two-dimensional gel electrophoresis and analyzed by computerized microdensitometry of autoradiographic patterns.
Type of method:
in vitro
Endpoint addressed:
carcinogenicity

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):
- Molecular formula (if other than submission substance): NaHSO3
- Molecular weight (if other than submission substance): 104.06 g/mol
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state:
- Analytical purity:
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material:
- Other:

Administration / exposure

Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1 mM NaHSO3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5 mM NaHSO3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
10 mM NaHSO3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
20 mM NaHSO3
Basis:
nominal conc.
No. of animals per sex per dose:
not applicable
Details on study design:
-Cells from a secondary culture were exposed 24 h after plating for 15 min to 20 mM sodium bisulfite in PBS (0, 1, 5, 10, or 20 mM).
- After being incubated for a total of 7 days, morphologically transformed colonies were ring isolated and expanded.
- Within 6 weeks cell populations were injected subcutaneously into nu/nu mice to determine tumorigenicity.
- Cell lines of proven malignancy but which had not been derived from tumours were used exclusively.
- Amino acid-labelled [14C]-polypeptides from neoplastic and non-transformed parental foetal cells were separated by two-dimensional gel electrophoresis and analyzed by computerized microdensitometry of autoradiographic patterns.

Results and discussion

Details on results:
- Approximately 1000 polypeptides from parental fibroblasts at population doublings ranging from 4 to 20 and those from colony-derived malignant cell lines were compared.
- Sodium bisulfite caused neoplastic transformation of HFC which was associated with qualitative and quantitative changes of the polypeptide pattern. Seven malignant lines exhibited 4 qualitative polypeptide changes: two polypeptides shifted slightly to the acidic side, one new polypeptide was observed, and one polypeptide was absent.
- The transformed bisulfite lines differed quantitatively from control cells in that 10-25% and 2-4% of the polypeptides had differences in expression greater than 2- and 4-fold, respectively. 21 specific polypeptides in all transformed lines had coordinate quantitative changes.
- Because bisulfite at neutral pH fails to induce any significant DNA changes at concentration that cause transformation, polypeptides expressed immediately or 48 h after bisulfite treatment were compared to those of non-treated controls, and no differences were found.
- No differences were found in the polypeptides expressed immediately or 48 hours after bisulfite treatment. Even though bisulfite does not induce detectable DNA changes or early post-treatment polypeptide changes in polypeptide expression, a consistent set of qualitative and quantitative changes were observed after transformation.
- The qualitative polypeptide changes found in the bisulfite-induced malignant lines were similar to those seen in a benzo(a)pyreneinduced malignant line (OBP).
- The results suggest that there is a convergence of pathways responsible for carcinogenesis independent of the nature of initiation

Applicant's summary and conclusion

Conclusions:
The results suggest that there is a convergence of pathways responsible for carcinogenesis independent of the nature of initiation.