Toxicity of selected cationic drugs in retinoblastomal cultures and in cocultures of retinoblastomal and retinal pigment epithelial cell lines.
Tamoxifen and toremifene are antiestrogenic drugs successfully used in the therapy of breast cancer. Rheumatoid arthritis and malaria have been treated with chloroquine for decades. Unfortunately, tamoxifen and chloroquine are reported to induce retinal changes as a side effect. We now studied the effects of tamoxifen, toremifene, and chloroquine on the viability of the human retinoblastomal cell line Y79, using the WST-1 test or measurement of the cellular ATP content. The studies were made on Y79 cell cultures and on cocultures of Y79 cells and retinal pigment epithelial cell line ARPE-19. The cocultures were used to clarify the effect of retinal pigment epithelium on toxicity to Y79 cells. In the coculture, the drugs were applied to ARPE-19 cells growing in the culture inserts on top of Y79 cells and the viability of ARPE-19 and Y79 cells was assessed separately. Tamoxifen, toremifene, and chloroquine reduced dose-dependently the viability of Y79 cells after 24-h exposure. The ARPE-19 cells proved to be protective after chloroquine exposure in the coculture. The results shed light on the toxicity of tamoxifen and chloroquine in Y79 cells in vitro. With the coculture we were able to simulate the in vivo route of chloroquine to the retina via the retinal pigment epithelium.
Mäenpää
Hanna
H
Cell Research Center, Medical School, University of Tampere, Tampere, Finland. hanna.maenpaa@uta.fi
Toimela
Tarja
T
Mannerström
Marika
M
Saransaari
Pirjo
P
Tähti
Hanna
H
D002412:Cations; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000633:toxicity*; D018920:Coculture Techniques; D020847:Estrogen Receptor Modulators / Q000633:toxicity; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects*; D012175:Retinoblastoma / Q000473:pathology*; D013629:Tamoxifen / Q000633:toxicity*; D017312:Toremifene / Q000633:toxicity*
D002412:Cations; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen; D017312:Toremifene; D002738:Chloroquine