Fluorouracil induces apoptosis and surface molecule modulation of peripheral blood leukocytes.
Little is known about the direct effect of chemotherapy on normal peripheral blood leukocytes (PBL) or its contribution to leukopenia. We examined 5'-fluorouracil's (5FU) effect on PBL apoptosis and adhesion molecules' expression in a single-drug solid-tumor model. Possible apoptosis mediators were examined. The study included 32 colorectal cancer patients; apoptosis was determined by annexin-V binding and light-scatter morphology before and after drug infusion. CD18, CD11a, CD11b, and CD63 membranal levels were assayed by flow cytometry. Apoptosis was increased post-5FU administration in neutrophils (PMN), monocytes and lymphocytes (P < 0.05). Levels of Fas receptor and activated caspase 3 did not vary indicating that the process was not mediated by caspase 3 in the timeframe studied. Reduced CD63 on monocytes and decreased CD18 expression on PMN and non-apoptotic monocytes were observed (P < or = 0.05). CD11a,b expression did not vary. Decreased CD18 and CD63 levels were demonstrated in apoptotic and non-apoptotic PBL implying a more direct association with the drug itself.
Department of Medicine, Sapir Medical Center, Kfar Saba, Tel-Aviv, Israel.
O
O
Kimhi
L
L
Drucker
A
A
Neumann
H
H
Shapiro
J
J
Shapira
S
S
Yarkoni
M
M
Lahav
J
J
Radnay
M
M
Lishner
D015703:Antigens, CD / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001773:Blood Cells; D018821:CD18 Antigens / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D007970:Leukopenia / Q000139:chemically induced; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D060149:Tetraspanin 30
D015703:Antigens, CD; D000970:Antineoplastic Agents; D018821:CD18 Antigens; C554586:CD63 protein, human; D015815:Cell Adhesion Molecules; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D005472:Fluorouracil