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Combinations of radiation and misonidazole in a murine lung tumor model. [/sup 137/Cs]

Journal Article · · Radiat. Res.; (United States)
DOI:https://doi.org/10.2307/3575513· OSTI ID:6460284
The response of KHT sarcoma cells growing as microscopic lung colonies to radiation treatments given with or without the hypoxic cell sensitizer misonidazole was evaluated using an in vivo to in vitro clonogenic cell survival assay. For comparison the survival curve for well-oxygenated KHT sarcoma cells was obtained by excising the colony-containing lungs from their hosts, dispersing the lung colonies to a single-cell suspension, and irradiating the cells in vitro. By increasing the time between excision and irradiation from 2 to 24 hr it was possible to demonstrate for these lung colony-derived cells an intercellular contact effect denoted by a reduction in the shoulder of the cell survival curve over this period. In vivo radiation treatments were given at two different lung colony volumes, 0.7 and 1.8 mm/sup 3/. The addition of misonidazole prior to irradiation sensitized the hypoxic cell compartment at both colony sizes and reduced the final slope in each case to the same degree (factor of approx. 1.8). At a cell survival level of 10/sup -3/ this resulted in an enhancement ratio of approx. 1.2 to approx. 1.5. By comparison this dose of misonidazole did not enhance the radiation-induced pulmonary toxicity determined using a LD/sub 50/180/ assay.
Research Organization:
Univ. of Rochester Medical Center, NY
OSTI ID:
6460284
Journal Information:
Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 86:2; ISSN RAREA
Country of Publication:
United States
Language:
English