The influence of the protector thiol L-cystein on the toxic and therapeutic responses of stabilized “activated” cyclophosphamide (4-(S-ethanol)-sulfido-cyclophosphamide) View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1984-06

AUTHORS

Georg Voelcker, Peter Laber, Helmut Rockinger, Carla Wientzek, Hans-Jürgen Hohorst

ABSTRACT

The influence of L-cystein on the toxic and therapeutic responses of 4-(S-ethanol)-sulfido-cyclophosphamide (P1), a stabilized "activated" cyclophosphamide, was investigated. Stabilized "activated" cyclophosphamides hydrolyze under physiological conditions to 4-hydroxycyclophosphamide (4-OH-CP). The antitumor activity of P1 was investigated on a heterotransplanted human bladder sarcoma in nude mice and in perfusion experiments carried out on the isolated tumor bearing limb in rats. Due to its rapid hydrolysis to 4-OH-CP, P1 exhibits severe local toxicity which is decreased by the protector thiol L-cystein. Simultaneous application of double molar amounts of L-cystein reduces toxicity in nude mice to approximately one-third. Therapeutic activity is not affected by this ratio of L-cystein so that the protector thiol increases the therapeutic efficacy of P1. Higher amounts of L-cystein reduce both the acute toxicity in nude mice and the therapeutic efficacy against the human xenograft. The perfusion experiments demonstrate that a P1 concentration necessary to cure rats with tumor bearing limb is only tolerated in combination with L-cystein. More... »

PAGES

253-259

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00232360

DOI

http://dx.doi.org/10.1007/bf00232360

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026117364

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/6469518


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