[Analysis of tumor cell growth and effects of antitumor drugs on cell cycle regulation by flow cytometry].
Relationship between tumor cell growth and cell cycle and influence of antitumor drugs on the cell cycle regulation were investigated by the use of murine EL-4 tumor. Cell growth curve of EL-4 cells was well related to the cell cycle pattern analyzed by two color flow cytometry both in vivo and in vitro. The ratio of S phase rapidly increased in early log phase and decreased from late log to plateau phases. The ratio of G0/G1 phase showed a reciprocal change. Minimum effective doses of 5-fluorouracil (5-FU) and CDDP on EL-4 growth in vitro were 1 x 10(-6) M and 0.5 micrograms/ml, respectively. At such doses, 5-FU showed an accumulation in early S phase and CDDP showed a partial synchronization in S phase and subsequent accumulation in late S and G2 + M phase. In case of in vivo administration with 5-FU (20 mg/kg/day) ratio of S phase was higher than in untreated control mice at day 2-3 but decreased rapidly thereafter. Mice administered with CDDP (5 mg/kg/day) showed a decrease in S phase from day 2 and completely rejected the tumors by day 5. From these results, each phase of cell cycle was influenced by the cell growth characteristics and the cell cycle pattern was dynamically changed according to the mode of action of antitumor drugs. Moreover, in vivo effects of these drugs can be evaluated adequately by the analysis of the cell cycle.
Shinomiya
N
N
Dept. of Microbiology, National Defense Medical College, Saitama, Japan.
Katsura
Y
Y
Tsugita
M
M
Noritake
M
M
Tsuru
S
S
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D007399:Interphase; D008223:Lymphoma / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D002945:Cisplatin; D005472:Fluorouracil