High-resolution localization of drug binding sites

Autor: Austin J. MacInnis, Steven F. Hoff
Rok vydání: 1981
Předmět:
Zdroj: Journal of Ultrastructure Research. 74:205-216
ISSN: 0022-5320
DOI: 10.1016/s0022-5320(81)80078-0
Popis: Previous attempts at the ultrastructural identification of drug binding sites have been thwarted by denaturation and extraction of the tissue, and unreliable specificity of the localization procedure. We minimized the first problem by using the low denaturation method reported by Sjostrand and Barajas (1968, J. Ultrastruct. Res. 25, 121). Specific and reliable localization of lucanthone and methylene blue in the Ehrlich Ascites Circinoma was accomplished by precipitation of the drugs with phosphotungstic acid a pH 7. Lucanthone was localized only in the heterochromatin and interchromatinic granules, which supports the biochemical reports of lucanthone binding to DNA. The useful light microscopic stain, methylene blue was localized also in nuclear locations such as: the nucleolus, heterochromatin, and interchromatinic granules. This new approach should have a wide application in the analysis of the subcellular distribution, toxicology, structure-activity relationships, and possible mechanism of action of various drugs.
Databáze: OpenAIRE