Uptake and intracellular distribution of idarubicin in secondary cultures of normal and neoplastic urothelium.
This study analyzes the uptake and endocellular distribution of idarubicin (IDA) in normal and neoplastic urothelial secondary cultures in relation to the changes in concentration and time of exposure. The urothelial lines were isolated by Freshney's method from biopsy fragments taken from five patients with superficial bladder cancer. Pharmacological experiments were carried out on subcultures previously immunophenotypically characterized and did not exceed ten passages. The uptake and endocellular distribution of IDA was analyzed by densitometric image analysis on cells treated for 10, 20, 30 and 60 min and 2 h with scalar dosages from 10 ng/ml to 2430 ng/ml. Microscopic observations and densitometric analyzes revealed that in the cells treated with IDA, fluorescence was higher in the cytoplasm compared to the nucleus and increased with the change in dosage. Moreover, densitometric data showed that IDA uptake in the first 20 min was higher in the neoplastic cells, but after that period its behavior became heterogeneous at 30 and 60 min, while at 2 h there was an inversion of the trend. These results suggest that the in vitro cytotoxicity should be evaluated in order to verify whether the elevated uptake of IDA in the first 20 min of treatment is really correlated to a more elevated toxicity in the neoplastic cells with respect to the normal cells. This is presently under investigation.
De Angeli
S
S
Cell Culture Laboratory, Treviso Hospital, Piazzale dell' Ospedale, Italy.
Buoro
S
S
Fandella
A
A
Anselmo
G
G
Belmonte
P
P
Zucconelli
R
R
Fiaccavento
G
G
Parnigotto
P P
PP
Stocco
F
F
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology; D001693:Biological Transport, Active; D002478:Cells, Cultured; D006801:Humans; D015255:Idarubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D015255:Idarubicin