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A Strategy to Identify Compounds that Affect Cell Growth and Survival in Cultured Mammalian Cells at Low-to-Moderate Throughput
Published on: September 22, 2019
Transformation of cell cultures as a parameter for detecting the potential carcinogenicity of antischistosomal drugs
Abstract:
Several antischistosomal drugs and their metabolites were found to transform rat embryo cell cultures persistently infected with the Rauscher leukemia virus. The transformed cells produced fibrosarcomas when implanted into newborn rats. Cell cultures treated with either virus or chemical alone were not transformed nor were they invasive in rats. The advantages of early screening of developmental drugs in cell culture systems are discussed.
Insights
Antischistosomal drugs and their metabolites can transform virus-infected rat cells, causing tumors in rats. Early cell culture screening is vital for developmental drug safety assessment.
Area of Science:
- Toxicology
- Oncology
- Virology
Background:
- Persistent viral infections, such as Rauscher leukemia virus, can alter cellular behavior.
- Drug development requires rigorous safety testing to identify potential carcinogens.
- Cell culture systems offer a model for studying viral-induced cell transformation.
Purpose of the Study:
- To investigate the potential of antischistosomal drugs and their metabolites to induce cell transformation.
- To evaluate the tumorigenicity of drug-transformed cells in vivo.
- To highlight the utility of cell culture for early drug screening.
Main Methods:
- Rat embryo cell cultures were persistently infected with Rauscher leukemia virus.
- Infection-permissive cell cultures were treated with antischistosomal drugs and their metabolites.
- Transformed cells were implanted into newborn rats to assess tumorigenicity and invasiveness.
Main Results:
- Several antischistosomal drugs and their metabolites induced persistent transformation in virus-infected rat cell cultures.
- Transformed cells, upon implantation into rats, produced fibrosarcomas.
- Neither the virus nor the chemicals alone caused cell transformation or invasiveness.
Conclusions:
- Antischistosomal drugs and their metabolites can act as potent oncogenic agents in the context of viral infection.
- Cell culture systems provide a valuable platform for the early detection of drug-induced oncogenesis.
- This study underscores the importance of comprehensive safety evaluations during drug development, particularly for compounds targeting infectious diseases.
