Time-and Concentration-Dependent Cytotoxicity of Ricin in Human Lung Epithelial Cells
DEFENCE SCIENCE AND TECHNOLOGY ORGANISATION VICTORIA (AUSTRALIA) HUMAN PROTECTION AND PERFORMANCE DIV
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Ricin, a potent ribosome-inactivating hetero-dimeric protein toxin 66kDa produced in the seeds of the castor bean plant Ricinus communis, is a Category B Agent on the Centres for Disease Control CDC Select Agent List. Using human small airway epithelial cells, this is the first study to investigate the time- and dose-dependent cytotoxic effects of ricin in a human cell line. Ricin 1- 100pM produced a time- and dose-dependent decrease in small airway epithelial cell survival. Ricin 10 and 100pM reduced cell survival to 57 and 50 respectively, after 12 hours exposure and to 12 cell survival after 24 hours exposure to the toxin. Washing cells after 1-5 minutes exposure to ricin 0.01-100pM prevented any significant ricin-induced SAE cell death. However, after washing cells exposed to ricin for 15 or 30 minutes, there was a significant reduction in SAE cell survival 84 and 71, respectively, for 10pM and 45 and 31, respectively, for 100pM. The results suggest that the binding of ricin to the cell surface and subsequent intracellular uptake and cell death appears to be irreversible by washing between 5 and 15 minutes following exposure to the toxin. There may be a window of opportunity for treatment, and therefore prevention, of some lung cell death up to 12 hours after aerosol exposure to ricin given that there was some survival of human lung cells after this time of exposure.
- Anatomy and Physiology
- Medicine and Medical Research