Modulation of the antioxidant activities in dox-sensitive and -resistant Friend leukemia cells. Effect of doxorubicin.
Tumor cell resistance to anthracyclines has been associated with increased activity against free radicals. Here, we have investigated the direct effect of doxorubicin (DOX) in the modulation of glutathione level and antioxidant activities in DOX-sensitive and-resistant cells (288 fold). The glutathione level in untreated cells was 88% greater in resistant than in sensitive cells. The activities of the superoxide dismutase, glutathione -S-transferase and glutathione reductase were respectively 24, 15 and 38% higher in resistant cells than in their sensitive counterparts. In contrast, catalase and total glutathione peroxidase were reduced in resistant cells by 18 and 21% respectively. Moreover, the activity of selenium-dependent glutathione peroxidase was lowered by 47% in the resistant as compared to the sensitive cells. Exposure of sensitive or resistant cells to low doses of DOX did not affect these levels in either cell variant. It is concluded therefore that resistance to anthracyclines may not always be associated with an elevated level of intracellular antioxidant activity enzymes.
Crescimanno
M
M
Istituto di Farmacologia, Policinico P. Giaccone, Palermo, Italy.
D'Alessandro
N
N
Armata
M G
MG
Toulmond
S
S
Tapiero
H
H
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology; D005622:Friend murine leukemia virus; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007942:Leukemia, Experimental / Q000201:enzymology*; D051379:Mice; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D007527:Isoenzymes; D004317:Doxorubicin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione