Abstract
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.
Similar content being viewed by others
References
Ames MM, Spreafico F (1992) Selected pharmacologic characteristics of idarubicin and idarubicinol. Leukemia 6:70
Boiron JM, Beloc F, Montastruc M, Cony-Makhoul P, Dumain P, Marit G, Mahon FX, Puntous M, Lopez F, Lacombe F, Reiffers J (1994) Flow cytometric study of idarubicin and daunorubicin accumulation and the effect of verapamil in leukemic cell lines and fresh cells from patients with acute nonlymphoblastic leukemia. Leukemia Res 18:313
Facchetti I, Grandi M, Cucchi P, Geroni C, Penco S, Vigevani (1991) Influence of lipophilicity on cytotoxicity of anthracyclines in LoVo and LoVo/Dx human cell lines. Anticancer Drug Design 6:385
Freshney RI (1987) Disaggregation of the tissue and primary culture. In: Freshney RI (ed) Culture of animal cells. AR Liss, New York, p 107
Gieseler F, Biersack H, Brieden T, Manderscheid J, NuBler V (1994) Cytotoxicity of anthracyclines: correlation with cellular uptake, intracellular distribution and DNA binding. Ann Hematol 69:613
Glantz SA (1988) Come verificare 1e differenze fra gruppi. In: Glanz SA (ed) Statistica per discipline bio-mediche. McGrawHill Libri Italia, Milan, p 29
Goebel M (1993) Oral idarubicin an anthracycline derivative with unique properties. Ann Hematol 66:33
Herr HW, Laudone VP (1989) Intravesical therapy for superficial bladder cancer. In: Ball TP (ed) AUA Update Series, vol. VIII. American Urological Association, Houston, p 90
Hollingshead LM, Faulds D (1991) Idarubicin, a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs 42:690
Minderman H, Buscaglia MD, Rustum YM (1994) Scheduledependent efficacy of idarubicin (ida) and doxorubicin (dox). Leukemia 8:1401
Mross K, Hamm K, Schultze-Seemann W, Burk K, Hossfeld DK (1992) Tissue disposition and plasma concentration of idarubicin after intravesical therapy in patients with bladder tumors. Cancer Chemother Pharmacol 29:490
Schultze-Seemann W, Mross K, Burk K, Sommerkamp H (1994) Intravesical idarubicin- a phase I study. Urol Res 22:95
Sehested M, Skovsgaard T, van Deurs B, Winthernielsen H (1987) Increased plasma membrane traffic in daunorubicin resistant P388 leukemic cells. Br J Cancer 56:747
Smith PJ, Rackstraw C, Cotter F (1994) DNA fragmentation as a consequence of cell cycle traverse in doxorubicin- and idarubicin-treated human lymphoma cells. Ann Hematol 69: S7-S11
Toffoli G, Simone F, Gigante M, Boiocchi M (1994) Comparison of mechanism responsible for resistance of idarubicin and daunorubicin in multidrug resistant LoVo cell lines. Biochem Pharmacol 48:1871
Union Internationale contre le Cancer (1987) TNM classification of malignant tumors, 4th edn. UICC, Geneva
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
De Angeli, S., Buoro, S., Fandella, A. et al. Uptake and intracellular distribution of idarubicin in secondary cultures of normal and neoplastic urothelium. Urol. Res. 25, 125–130 (1997). https://doi.org/10.1007/BF01037928
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01037928