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(PP211) A bystander effect in alpha-particle irradiations of human prostate tumor cells.
Wang, Rong1, 2, Coderre, Jeffrey*,1, 1 Department of Nuclear Science and Engineering, Cambridge, MA, USA2 Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA
ABSTRACT- The objective of these studies is to determine whether a bystander effect in tumor cells can be exploited to improve the overall uniformity and extent of tumor cell kill during alpha-particle-based therapy. An apparatus for alpha-particle irradiation of cells growing as a monolayer on a 1.4 um-thick Mylar membrane directly above an americium-241 alpha-particle source was constructed and calibrated. The alpha-particle fluence was 998 counts/mm2/sec, the average alpha-particle energy was 3.14 MeV, the average linear energy transfer was 128 keV/um, and the average dose rate to the cells was 1.2 Gy/min. A co-culture system was used to create two populations of DU-145 human prostate carcinoma cells that shared the same medium: 1) cells growing on the Mylar membrane and directly irradiated with alpha particles, and 2) cells growing on an insert, well beyond the range of the alpha particles. The irradiated DU-145 cells released a soluble factor(s) into the medium, which caused a bystander effect (a 50% increase in micronucleus formation relative to controls) in the non-targeted tumor cells growing on the insert. Chemical scavenger and medium-transfer experiments indicate that a short-lived radical species is involved. Cells on the insert had to be present during the irradiation of the targeted cells on the Mylar membrane for expression of this bystander effect. Addition of the radical scavenger DMSO to the medium during the irradiation completely blocked the bystander effect, whereas, addition of a nitric oxide scavenger had no effect. Pre-treatment of the tumor cells on the insert with Taxol produced an additive, or possibly synergistic, effect when combined with the bystander effect treatment that was dependent on the concentration of Taxol used. The results with Taxol suggest that DU-145 cells in the G2/M phase of the cell cycle are more sensitive to the bystander signal than those in G0/G1 phase.
Key words: bystander effect, tumor, alpha particles, radical
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