Protection by WR-2721 against radiation plus cis-diamminedichloroplatinum II caused injury to colonic epithelium in mice
- Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
The study was designed to investigate the ability of S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721) to protect mouse colon mucosa against damage produced by combined radiation plus cis-diamminedichloroplatinum II (cis-DDP) treatment. Mucosal damage was quantified by using the microcolony assay, which measures the survival of epithelial cells in colon crypts. Radiation doses ranged from 8-24 Gy gamma rays. Cis-DDP at a dose of 13 mg/kg and WR-2721 at a dose of 400 mg/kg body weight were given IP before or after irradiation. Addition of cis-DDP to radiation within 24 h before and 48 h after irradiation reduced the number of crypt cells more than did radiation alone. The highest reduction was seen when the drug was given 2 or 6 h before irradiation: the damage was increased by a factor of 1.5. Protective effects of WR-2721 were tested in the radiation plus cis-DDP combination in which cis-DDP was given 2 h before or 2 h after radiation. In the former sequencing, WR-2721 was given 30 min before radiation (90 min after cis-DDP); damage was reduced more than the amount of damage contributed by cis-DDP. When cis-DDP was given 2 h after irradiation, WR-2721 was administered 30 min either before irradiation or 30 min before cis-DDP. Here, the protective effect was achieved only when WR-2721 was given before radiation: the PF was 1.3 in that case and only 1.1 when WR-2721 was given before cis-DDP. Thus, WR-2721 must be given before irradiation, but even the degree of protection achieved depends on whether cis-DDP is applied before or after irradiation, with the protection being greater in the former situation. Observations showed that WR-2721 is a potent protector against the injury of mouse colon mucosa produced by the combined radiation plus cis-DDP treatment. 23 refs., 2 figs.
- OSTI ID:
- 6581679
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics; (United States), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States) Vol. 28:4; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CARBOXYLIC ACIDS
COMBINED THERAPY
CRYPT CELLS
ESTERS
MAMMALS
MICE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHORIC ACID ESTERS
RADIATION EFFECTS
RODENTS
SIDE EFFECTS
SOMATIC CELLS
THERAPY
THIOLS
VERTEBRATES