The effects of doxorubicin on apoptosis and adhesion molecules of normal peripheral blood leukocytes-an ex vivo study.
This ex vivo study was designed to evaluate the effect of doxorubicin (Dox) on normal peripheral blood leukocytes (PBL) in terms of apoptosis and membranal expression levels of adhesion molecules. Blood was drawn immediately prior to and after Dox administration from 21 breast cancer patients, and incubated at room temperature for 24 h. Flow cytometry was employed in analysis of apoptosis with Annexin-V and protein membranal expression levels with monoclonal antibodies to CD49d, CD18, CD11a-c and CD63. Dox induced statistically significant apoptosis in all three major PBL subpopulations (p<0.01). Between 70 and 90% of samples underwent apoptosis in all PBL subgroups. No significant change was observed in the membranal level of CD63, CD49d and CD11a-c after chemotherapy in any PBL subpopulation. However, a significant reduction in the membranal level of CD18 was demonstrated in polymorphonuclear cells after Dox (p<0.005) both in apoptotic and non-apoptotic cells (p<0.05), suggesting a direct effect of Dox rather than an apoptosis-associated phenomenon. We observed the expected leukopenia 10 days after Dox administration with no correlation to apoptosis, suggesting that leukopenia by Dox is largely attributed to toxicity of blood progenitors.
Ciobotaro
Pnina
P
Oncogenetics Laboratory and Department of Medicine, Sapir Medical Center, Kfar-Saba, Israel.
Drucker
Liat
L
Neumann
Avivit
A
Shapiro
Hava
H
Shapira
Jermey
J
Radnay
Judith
J
Lishner
Michael
M
D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D017304:Annexin A5; D000903:Antibiotics, Antineoplastic; D015815:Cell Adhesion Molecules; D005456:Fluorescent Dyes; D004317:Doxorubicin; D016650:Fluorescein-5-isothiocyanate