- Tytuł:
- The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia.
- Autorzy:
-
Styczyński, Jan
Wysocki, Mariusz
Dębski, Robert
Kurylak, Andrzej
Balwierz, Walentyna
Rokicka-Milewska, Roma
Matysiak, Michał
Balcerska, Anna
Kowalczyk, Jerzy
Wachowiak, Jacek
Sońta-Jakimczyk, Danuta
Chybicka, Alicja - Powiązania:
- https://bibliotekanauki.pl/articles/1043814.pdf
- Data publikacji:
- 2002
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
P-glycoprotein
acute myeloblastic leukemia
anthracyclines
acute lymphoblastic leukemia
drug resistance - Opis:
- Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.
- Źródło:
-
Acta Biochimica Polonica; 2002, 49, 1; 99-107
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł