Cytotoxicity of daunorubicin in trisomic (+21) human fibroblasts: relation to drug uptake and cell membrane fluidity.

Abstract:

:The influence of daunorubicin (DNR) on survival of human normal (S-126) and trisomic, with respect to chromosome 21 (T-164; S-240), skin fibroblasts and some parameters related to it, such as intracellular drug accumulation, distribution and interaction with cell membrane, were studied. The in vitro growth-inhibition assay indicated that DNR was less cytotoxic for trisomic than for normal cells. Comparison of kinetic parameters and intracellular distribution of this compound showed that the uptake and the amount of intracellular free DNR were greater in normal than in trisomic cells. Contrary to this, there were no significant differences between the amount of DNA-bound drug in both types of cells. TMA-DPH and 12-AS fluorescence anisotropy measurements demonstrated that DNR decreased lipid fluidity in the inner hydrophobic region of plasma membrane in both cell types, but did not influence the fluidity of the outer surface of membrane. We conclude that fibroblasts derived from individuals affected with Down's syndrome are better protected from the damage induced by DNR than normal cells.

journal_name

Cell Biol Int

authors

Przybylska M,Koceva-Chyla A,Rózga B,Józwiak Z

doi

10.1006/cbir.2000.0583

keywords:

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

157-70

issue

2

eissn

1065-6995

issn

1095-8355

pii

S1065-6995(00)90583-3

journal_volume

25

pub_type

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