Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide.
OBJECTIVE
Breast carcinoma is related to the increase of lipid peroxidation in plasma with concomitant decrease of antioxidant (AO) defense capacity in blood cells, which becomes more pronounced during aging of the patients. This work evaluated the potential age-related effect of chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) on the level of lipid hydroperoxides (LP), glutathione (GSH), AO enzyme activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in breast cancer patients. The level of CuZnSOD protein was assessed after the FAC therapy and radiotherapy of breast cancer.


METHODS
AO parameters were measured in the blood of 58 breast cancer patients and 60 healthy age-matched healthy subjects by biochemical and Western blot analyses.


RESULTS
Increased oxidative stress (LP: p<0.05) and decreased AO enzyme activities (CuZnSOD: p<0.01, GPx: p<0.05, GR: p<0.01) and GSH level (p<0.01) in the blood of breast cancer patients in response to FAC chemotherapy seem not to be age-dependent. CuZnSOD enzyme expression decreased after the FAC chemotherapy (p<0.05), while it increased after the radiotherapy of breast cancer (p<0.05).


CONCLUSIONS
FAC chemotherapy and radiotherapy promote further oxidative shift, which potentiate already existing chronic oxidative stress linked to breast cancer. In these effects, impaired capacity for H(2)O(2) detoxification (CAT, GPX and GSH) seems to have major contribution.
Kasapović
Jelena
J
Laboratory of Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. jelkas@vinca.rs
Pejić
Snežana
S
Stojiljković
Vesna
V
Todorović
Ana
A
Radošević-Jelić
Ljiljana
L
Saičić
Zorica S
ZS
Pajović
Snežana B
SB
D000368:Aged; D000375:Aging / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000097:blood; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008875:Middle Aged; D013482:Superoxide Dismutase / Q000097:blood
D000970:Antineoplastic Agents; D000975:Antioxidants; D004317:Doxorubicin; D003520:Cyclophosphamide; D013482:Superoxide Dismutase; D005978:Glutathione; D005472:Fluorouracil