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Testing of New Hypoxic Cell Sensitizers in Vivo

Helen B. Stone and Mark S. Sinesi
Radiation Research
Vol. 91, No. 1 (Jul., 1982), pp. 186-198
DOI: 10.2307/3575826
Stable URL: http://www.jstor.org/stable/3575826
Page Count: 13
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Testing of New Hypoxic Cell Sensitizers in Vivo
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Abstract

We tested five agents as potential sensitizers of hypoxic cells in vivo in mammary tumors in C3H mice in comparison with misonidazole. The ${\rm LD}_{50/2}$ for desmethylmisonidazole was 2.7 mg/g body wt, compared to 1.3 for misonidazole. It was as effective in reducing the ${\rm TCD}_{50}$ of MDAH-MCa-4 as were equitoxic doses of misonidazole. The ${\rm LD}_{50/2}$ of SR-2508 was 3.3 mg/g and was as effective a sensitizer as misonidazole. Ro 07-0741 was more toxic, with an ${\rm LD}_{50/2}$ of 0.6 mg/g, but was as effective as misonidazole at equitoxic doses. NP-1 was also more toxic than misonidazole (${\rm LD}_{50/2}=0.4\ {\rm mg}/{\rm g}$) but was a less effective sensitizer. Rotenone, which causes sensitization by inhibiting cellular respiration, thus increasing the diffusion distance of oxygen, was extremely toxic (${\rm LD}_{50/2}=0.003\ {\rm mg}/{\rm g}$), and systemic respiratory inhibition and the radioprotective effects of the dimethyl sulfoxide used to dissolve it rendered it totally ineffective as a sensitizer in vivo.

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