PMID- 10810382
OWN - NLM
STAT- MEDLINE
DCOM- 20000601
LR  - 20131121
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 20
IP  - 2A
DP  - 2000 Mar-Apr
TI  - Polyploidization induced by acridine orange in mouse osteosarcoma cells.
PG  - 965-70
AB  - This study was undertaken to clarify the in vitro effect of acridine orange (AO) 
      on the cell kinetics of mouse osteosarcoma cells, as well as the mechanism of 
      cell growth inhibition induced by AO. A mouse osteosarcoma cell line (MOS), 
      established from a radiation-induced mouse osteosarcoma, was cultured under 
      exposure to 0.05, 0.5, 5, and 50 micrograms/ml of AO, either continuously or for 
      10 minutes. The cell kinetic analysis was performed using the following 
      parameters: tumor cell growth by trypan blue exclusion test, mitotic activity, 
      DNA synthetic activity by BrdU labeling and DNA ploidy by cytofluorometry. The 
      results showed that continuous exposure to 5 and 50 micrograms/ml of AO or 10 
      minute exposure to 50 micrograms/ml of AO quickly killed the tumor cells within 
      12 hours, whereas continuous exposure to 0.5 microgram/ml of AO or 10 minute 
      exposure to 5 micrograms/ml of AO gradually inhibited tumor cell growth. Under 
      the latter conditions, mitotic activity was rapidly and completely inhibited 
      within 48 hours but DNA synthetic activity was not completely inhibited even 
      after 96 hours. DNA ploidy analysis demonstrated that most of the tumor cells 
      arrested at the S-G2 phase after 12 hours, followed by G2 phase arrest after 24 
      hours and progressive DNA synthesis to a higher DNA ploidy class after 48 to 96 
      hours. We therefore concluded that a high concentration of AO has a strong 
      cytocidal effect due to cytotoxicity whilst a moderate concentration of AO 
      induces progressive and synchronous polyploidization by mitotic inhibition 
      without DNA damage in MOS cells. We presume that this in vitro effect on MOS 
      cells may be caused by protein synthetic inhibition after transfer RNA 
      inactivation caused by AO binding.
FAU - Kusuzaki, K
AU  - Kusuzaki K
AD  - Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, 
      Japan.
FAU - Takeshita, H
AU  - Takeshita H
FAU - Murata, H
AU  - Murata H
FAU - Gebhardt, M C
AU  - Gebhardt MC
FAU - Springfield, D S
AU  - Springfield DS
FAU - Mankin, H J
AU  - Mankin HJ
FAU - Ashihara, T
AU  - Ashihara T
FAU - Hirasawa, Y
AU  - Hirasawa Y
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (DNA, Neoplasm)
RN  - F30N4O6XVV (Acridine Orange)
SB  - IM
MH  - Acridine Orange/*toxicity
MH  - Animals
MH  - Bone Neoplasms/genetics
MH  - Cell Division/drug effects
MH  - DNA, Neoplasm/biosynthesis/genetics
MH  - Dose-Response Relationship, Drug
MH  - Kinetics
MH  - Mice
MH  - Mitosis/drug effects
MH  - Mitotic Index/drug effects
MH  - Neoplasms, Radiation-Induced/genetics
MH  - Osteosarcoma/genetics
MH  - *Polyploidy
MH  - Tumor Cells, Cultured
EDAT- 2000/05/16 09:00
MHDA- 2000/06/03 09:00
CRDT- 2000/05/16 09:00
PHST- 2000/05/16 09:00 [pubmed]
PHST- 2000/06/03 09:00 [medline]
PHST- 2000/05/16 09:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2000 Mar-Apr;20(2A):965-70.