Jan 24, 2007

Efficacy of increasing the therapeutic index of irinotecan, plasma and tissue selenium concentrations is methylselenocysteine dose dependent

Biochemical Pharmacology
Rami G AzrakYoucef M Rustum

Abstract

This study was designed to understand the basis for the efficacy of methylselenocysteine (MSC) in increasing the therapeutic index of irinotecan against human tumor xenografts. Nude mice bearing human head and neck squamous cells carcinoma xenografts (FaDu and A253) were treated orally with different doses of MSC and irinotecan. Plasma, tumor and normal tissue samples were collected at different times after MSC treatments and were analyzed for selenium (Se) concentration using electrothermal atomic absorption spectrophotometry. MSC is highly effective in modulating the therapeutic index of irinotecan. Enhanced irinotecan efficacy was greater in FaDu tumors (100% CR) than in A253 tumors (60% CR), and depended on MSC dose with a minimum effective dose of 0.01 mg/dx28. The highest plasma Se concentration was achieved 1h after a single dose and 28 d after daily treatments of MSC. The ability of FaDu tumors to retain Se was significantly better than A253 tumors, and the highest Se concentration in normal tissue was achieved in the liver. Peak plasma and tissue Se concentrations were functions of the dose and duration of MSC treatment. The MSC-dependent increase in Se level in normal tissues may contribute to the protective effect ag...Continue Reading

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References

Mentioned in this Paper

Irinotecan hydrochloride
Squamous Epithelial Cell
Fluorouracil
Selenium
Large Intestine
Selenomethylselenocysteine, (L)-isomer, 75Se-labeled
Procedures on Large Intestine
L-Selenomethionine
Selenite
Organoselenium Compounds

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