Development of human epithelial cell systems for radiation risk assessment

Area of Science:

• Astrobiology and Space Medicine
• Radiation Biology
• Cellular and Molecular Oncology

Background:

• Cancer induction is a primary health concern for astronauts due to space radiation exposure.
• Understanding the carcinogenic effects of heavy ions on human cells is critical for radiation risk assessment.
• Existing cell models may not fully capture the complexities of human cellular response to space radiation.

Purpose of the Study:

• To develop and utilize a human mammary epithelial cell system for in vitro studies of neoplastic transformation.
• To investigate the effects of heavy ion and high-linear energy transfer (LET) radiation on human epithelial cells.
• To establish a reliable in vitro model for assessing the carcinogenic potential of space radiation.

Main Methods:

• Development of an immortalized human mammary epithelial cell line.
• Irradiation of cells with heavy ions to obtain growth variants.
• Subsequent irradiation of growth variants with high-LET radiation to induce neoplastic transformation.
• Characterization of growth variants for anchorage-dependent growth and density inhibition.

Main Results:

• Cloned growth variants were successfully obtained from heavy ion-irradiated immortal mammary cells.
• These variants maintained normal growth properties but exhibited transformed foci upon further high-LET irradiation.
• Neoplastic transformation of human epithelial cells appears to require multiple radiation exposures ('multihits').

Conclusions:

• Human epithelial cells exhibit high genomic stability, necessitating multiple radiation exposures for neoplastic transformation.
• The developed growth variants serve as a valuable in vitro model system for space flight experiments.
• This model can aid in determining the carcinogenic effects of space radiation on human epithelial cells.