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Title: Ocular penetration, toxicity, and radiosensitization effects of two hypoxic cell radiosensitizers on retinoblastoma

Abstract

Two new radiosensitizing drugs, SR-2508 and SR-2555, were studied for their in vivo toxicity and absorption properties. For both drugs, 100 mg dissolved in 0.5 mL of normal saline resulted in the maximum acceptable level of toxicity when injected subconjunctivally in rabbit eyes as determined by ocular and histopathologic changes. SR-2508 showed higher ocular and systemic absorption than SR-2555. The radiosensitizing ability of these drugs was studied using Chinese hamster ovary cells and the retinoblastoma cell line, V79c6. Results of the in vitro radiation experiments indicate that both drugs are comparable with misonidazole in their radiosensitizing ability, with SR-2508 being slightly more effective than SR-2555. Because of their relative high ocular absorption and low toxicity in comparison with misonidazole, these two drugs, particularly SR-2508, may be of clinical value and could be considered for adjunctive use as radiosensitizers of hypoxic tumors such as retinoblastoma.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Univ. of British Columbia, Vancouver
OSTI Identifier:
6914515
Resource Type:
Journal Article
Journal Name:
Arch. Ophthalmol. (Chicago); (United States)
Additional Journal Information:
Journal Volume: 11
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; RADIOSENSITIZERS; RADIOSENSITIVITY EFFECTS; TOXICITY; ANOXIA; CHO CELLS; EYES; NEOPLASMS; RABBITS; TESTING; ANIMAL CELLS; ANIMALS; BODY; BODY AREAS; DISEASES; DRUGS; FACE; HEAD; MAMMALS; ORGANS; SENSE ORGANS; VERTEBRATES; 560152* - Radiation Effects on Animals- Animals; 560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture

Citation Formats

Rootman, J, Gallie, B, Kumi, C, Bussanich, N, Rogers, B, and Palcic, B. Ocular penetration, toxicity, and radiosensitization effects of two hypoxic cell radiosensitizers on retinoblastoma. United States: N. p., 1986. Web. doi:10.1001/archopht.1986.01050230131048.
Rootman, J, Gallie, B, Kumi, C, Bussanich, N, Rogers, B, & Palcic, B. Ocular penetration, toxicity, and radiosensitization effects of two hypoxic cell radiosensitizers on retinoblastoma. United States. https://doi.org/10.1001/archopht.1986.01050230131048
Rootman, J, Gallie, B, Kumi, C, Bussanich, N, Rogers, B, and Palcic, B. 1986. "Ocular penetration, toxicity, and radiosensitization effects of two hypoxic cell radiosensitizers on retinoblastoma". United States. https://doi.org/10.1001/archopht.1986.01050230131048.
@article{osti_6914515,
title = {Ocular penetration, toxicity, and radiosensitization effects of two hypoxic cell radiosensitizers on retinoblastoma},
author = {Rootman, J and Gallie, B and Kumi, C and Bussanich, N and Rogers, B and Palcic, B},
abstractNote = {Two new radiosensitizing drugs, SR-2508 and SR-2555, were studied for their in vivo toxicity and absorption properties. For both drugs, 100 mg dissolved in 0.5 mL of normal saline resulted in the maximum acceptable level of toxicity when injected subconjunctivally in rabbit eyes as determined by ocular and histopathologic changes. SR-2508 showed higher ocular and systemic absorption than SR-2555. The radiosensitizing ability of these drugs was studied using Chinese hamster ovary cells and the retinoblastoma cell line, V79c6. Results of the in vitro radiation experiments indicate that both drugs are comparable with misonidazole in their radiosensitizing ability, with SR-2508 being slightly more effective than SR-2555. Because of their relative high ocular absorption and low toxicity in comparison with misonidazole, these two drugs, particularly SR-2508, may be of clinical value and could be considered for adjunctive use as radiosensitizers of hypoxic tumors such as retinoblastoma.},
doi = {10.1001/archopht.1986.01050230131048},
url = {https://www.osti.gov/biblio/6914515}, journal = {Arch. Ophthalmol. (Chicago); (United States)},
number = ,
volume = 11,
place = {United States},
year = {Sat Nov 01 00:00:00 EST 1986},
month = {Sat Nov 01 00:00:00 EST 1986}
}