Abstract
The ability of WR-2721 [S-2(3-aminopropylamino)ethyl-phosporothioic acid] to selectively protect the host against the toxic effects of multiple doses of cis-dichlorodiammineplatinum [cis-Pt] or cyclophosphamide [CY] has been studied in mice and rats bearing 3 different tumours. Selective protection against cis-Pt induced nephrotoxicity has been demonstrated under all conditions studied, with the extent of protection being inversely related to the size of the cis-Pt dose. For example, pre-treatment with 200 mg/kg of WR-2721 30 min before each weekly dose of 2 mg/kg of cis-Pt allows the administration of this cytotoxic agent for 3 times longer before nephrotoxic injury. In none of these studies was there tumour protection. The same pattern was observed with CY, but quantitation of the extent of marrow protection was not possible for the multiple treatment studies, due to the longer latent period between induced and observed death with this drug. We conclude, therefore, that for both of these drugs, selective protection of the kidney and marrow is not only maintained under conditions of multiple treatment, but actually enhanced due to the need for smaller doses of cytotoxic agents in these protocols.
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- Jordan S. W., Yuhas J. M., Key C. R., Hogstrom K. R., Butler J. L., Kligerman M. M. Comparative late effects of X-rays and negative pimesons on the mouse kidney. Am J Pathol. 1979 Nov;97(2):315–326. [PMC free article] [PubMed] [Google Scholar]
- Utley J. F., Marlowe C., Waddell W. J. Distribution of 35S-labeled WR-2721 in normal and malignant tissues of the mouse1,2. Radiat Res. 1976 Nov;68(2):284–291. [PubMed] [Google Scholar]
- Utley J. F., Phillips T. L., Kane L. J., Wharam M. D., Wara W. M. Differential radioprotection of euoxic and hypoxic mouse mammary tumors by a thiophosphate compound. Radiology. 1974 Jan;110(1):213–216. doi: 10.1148/110.1.213. [DOI] [PubMed] [Google Scholar]
- Ward J. M., Fauvie K. A. The nephrotoxic effects of cis-diammine-dichloroplatinum (II) (NSC-119875) in male F344 rats. Toxicol Appl Pharmacol. 1976 Dec;38(3):535–547. doi: 10.1016/0041-008x(76)90185-x. [DOI] [PubMed] [Google Scholar]
- Washburn L. C., Carlton J. E., Hayes R. L. Distribution of WR-2721 in normal and malignant tissues of mice and rats bearing solid tumors: dependence on tumor type, drug dose and species. Radiat Res. 1974 Aug;59(2):475–483. [PubMed] [Google Scholar]
- Yuhas J. M. A more general role for WR-2721 in cancer therapy. Br J Cancer. 1980 May;41(5):832–834. doi: 10.1038/bjc.1980.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yuhas J. M. Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-aminopropylamino)-ethylphosphorothioic acid. Cancer Res. 1980 May;40(5):1519–1524. [PubMed] [Google Scholar]
- Yuhas J. M., Culo F. Selective inhibition of the nephrotoxicity of cis-dichlorodiammineplatinum(II) by WR-2721 without altering its antitumor properties. Cancer Treat Rep. 1980 Jan;64(1):57–64. [PubMed] [Google Scholar]
- Yuhas J. M. Differential protection of normal and malignant tissues against the cytotoxic effects of mechlorethamine. Cancer Treat Rep. 1979 Jun;63(6):971–976. [PubMed] [Google Scholar]
- Yuhas J. M., Tarleton A. E., Harman J. G. In vitro analysis of the response of multicellular tumor spheroids exposed to chemotherapeutic agents in vitro or in vivo. Cancer Res. 1978 Nov;38(11 Pt 1):3595–3598. [PubMed] [Google Scholar]
- Yuhas J. M., Tarleton A. E., Molzen K. B. Multicellular tumor spheroid formation by breast cancer cells isolated from different sites. Cancer Res. 1978 Aug;38(8):2486–2491. [PubMed] [Google Scholar]