Influence of interleukin-2 infusion on cell cycle kinetics in the Walker-256 carcinosarcoma.
The effect of recombinant human interleukin-2 (IL-2) on tumor cell cycle kinetics was evaluated in rats bearing the Walker-256 carcinosarcoma. Seven days after implantation, tumor-bearing rats were infused intravenously with IL-2 at a dose of 500 mg/kg body weight or 5% dextrose for 6 h. Tumor cell mean DNA synthesis time (TDNA), labeling index, potential doubling time (Tpot), and growth fraction (GF) were determined in vivo by use of bromodeoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis using flow cytometry. IL-2 treatment significantly reduced the relative number of S-phase cells by 11.9% and increased the number of cells in the G0/G1 phase by 9.4%. The labeling index was reduced from 41.3 +/- 2.5% to 32.7 +/- 1.2% (P < .01). Estimates of TDNA derived from the change in BrdUrd movement relative to DNA content were not affected by IL-2 treatment. Based on these cytokinetic changes, IL-2 infusion significantly increased tumor Tpot from 15.3 +/- 0.3 h to 21.5 +/- 0.2 h (P < .001) and reduced GF from 1.01 +/- 0.07 to 0.83 +/- 0.01 (P < 0.001). The inhibitory effect of IL-2 infusion on tumor cell growth, which may be either direct or secondarily mediated by other factors, contrasts with other stimulatory effects of this cytokine on lymphoid cell proliferation.
Wan
J M
JM
Laboratory of Nutrition/Infection, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
Bistrian
B R
BR
Figoni
M A
MA
Istfan
N W
NW
D000818:Animals; D002279:Carcinoma 256, Walker / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D005434:Flow Cytometry; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008433:Mathematics; D008940:Mitotic Index / Q000187:drug effects; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley
D004273:DNA, Neoplasm; D007376:Interleukin-2