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Failla Memorial Lecture. From beans to genes--back to the future
1Center for Radiological Research, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Radiation Research
|March 1, 1992
Summary
Radiation biology research advanced mammalian cell killing by studying dose-rate effects, leading to new brachytherapy. Hypoxic cell sensitizers and in vitro oncogenic transformation assays were also developed.
Area of Science:
- Radiation Biology
- Cellular Biology
- Oncology
Background:
- Review of 35 years of radiation research focusing on dose-rate effects, hypoxic cell sensitizers, and in vitro oncogenic transformation.
- Initial work demonstrated mammalian cell killing dependence on gamma-ray dose rate, influencing brachytherapy development.
- Exploration of hypoxic tumor cell radiosensitization and bioreductive drugs, including misonidazole's cytotoxicity and thiol depletion mechanism.
Discussion:
- Investigated the role of hypoxic cells in limiting tumor curability by gamma rays.
- Developed nitromidazoles as hypoxic cell sensitizers and explored new generations of hypoxic cell cytotoxins.
- Assessed oncogenicity in relation to drug structure for novel therapeutic agents.
Key Insights:
- Demonstrated dose-rate dependence of mammalian cell killing by gamma rays, leading to pulsed low-dose-rate brachytherapy.
- Identified misonidazole as cytotoxic to hypoxic cells, with sensitization linked to thiol depletion.
- Established radiation-induced oncogenic transformation in vitro is mediated by a dominant transforming gene.
Outlook:
- Development of pulsed low-dose-rate brachytherapy and new clinical machines.
- Continued development of novel hypoxic cell cytotoxins with assessment of oncogenicity.
- Characterization and sequencing of a dominant transforming gene involved in radiation-induced oncogenic transformation.