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The induction of Ouar-mutations in nontransformable CVP3SC6 mouse fibroblasts
Abstract:
A line of C3H mouse fibroblasts designated CVP3SC6 (CVP) was found to be nonresponsive to the induction of morphological transformation by the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) and its BaP-7,8-diol and BaP-diol-epoxide derivates. This cell line was, however, susceptible to BaP-induced mutation to ouabain resistance (Ouar). Concentrations of BaP between 0.63 and 5 microM caused an 11- to 370-fold increase in the frequency of Ouar cells relative to that found in untreated cultures. Isolates of Ouar cells were at least 10,000-fold more resistant to the cytotoxic effects of Oua and exhibited a stable resistant phenotype after 120 days of growth in the absence of the selective agent.
Insights
This study found that CVP3SC6 mouse fibroblasts are resistant to benzo[a]pyrene (BaP)-induced transformation but susceptible to BaP-induced mutation. The cell line showed a stable resistance to ouabain after BaP exposure.
Area of Science:
- Cell biology
- Toxicology
- Carcinogenesis
Background:
- Polycyclic aromatic hydrocarbons (PAHs) like benzo[a]pyrene (BaP) are environmental mutagens.
- Cellular responses to PAHs can include morphological transformation and mutation.
- Understanding differential cellular responses to carcinogens is crucial for risk assessment.
Purpose of the Study:
- To investigate the response of a specific mouse fibroblast cell line (CVP3SC6) to benzo[a]pyrene (BaP).
- To determine if CVP3SC6 cells undergo morphological transformation or mutation when exposed to BaP and its derivatives.
- To characterize the resistance phenotype induced by BaP.
Main Methods:
- Exposure of CVP3SC6 mouse fibroblasts to varying concentrations of benzo[a]pyrene (BaP) and its derivatives.
- Assessment of morphological transformation induction.
- Measurement of mutation frequency to ouabain resistance (Ouar).
- Evaluation of ouabain cytotoxicity and stability of the resistant phenotype.
Main Results:
- CVP3SC6 cells were nonresponsive to BaP-induced morphological transformation.
- BaP exposure significantly increased mutation frequency to ouabain resistance (11- to 370-fold).
- Ouabain-resistant (Ouar) isolates showed >10,000-fold resistance to ouabain cytotoxicity and maintained this phenotype for 120 days.
Conclusions:
- The CVP3SC6 cell line exhibits a differential response to BaP, being resistant to transformation but susceptible to mutation.
- BaP is a potent mutagen in this fibroblast cell line, inducing stable ouabain resistance.
- This suggests distinct molecular pathways govern BaP-induced transformation and mutation in C3H mouse fibroblasts.