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217 The effects of tamoxifen on glutamate uptake by retinal pigment epithelium
Author(s) -
Mäenpää H.,
Toimela T.,
Saransaari P.,
Salminen L.,
Tähti H.
Publication year - 1996
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/0736-5748(96)80406-0
Subject(s) - citation , library science , retinal pigment epithelium , tamoxifen , computer science , biology , retinal , medicine , ophthalmology , genetics , cancer , breast cancer
Toxic drug concentrattons in virro are hard to estimate compared to in viva conditions. The composition of cell growth medium is of major importance in vitro. We examined the effect of two different growth media on drug response in retinal pigment epithelial (RPE) cell culture. The activity of lysosomal enzymes cathepsin D and N-acetyl-P-D-glucosamlnidase and cytosolic lactate dehydrogenase was measured after exposure in Dulbecco’s medium contaming normal fetal calf strum and after exposure in protein-stripped serum containing medium. The drugs used were tamoxifen. toremifene and chloroquine. Usual therapeutic doses of tamoxifen and toremifcne produce serum levels around 0.55 PM. The therapeutic dose of chloroquine results in serum levels of 0.8-2.5 PM. Tissue levels of tamoxifen and toremtfene are Sto ItM-fold higher than serum levels. High affinity and ac,cumulation of chloroquine to melanin causes high RPE-concentrations. Thus we chose the test concentrations between I and 40 PM. Our results support the view that tamoxifen, toremifene and chloroquine are avidly bound to calf serum proteins in the culture media. The efficacy of the drugs tested was diminished in serum containing medium. The medium with charcoal-stripped fetal calf serum made the the drugs more effective. As a conclusion careful consideration is recommended when applying in vifro cell cultures in estimating effective or toxtc doses of drugs. DIETARY IRON STATUS AND THE INTEGRITY OF THE DEVELOPING BRAIN