PMID- 2471903
OWN - NLM
STAT- MEDLINE
DCOM- 19890720
LR  - 20131121
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 3
IP  - 7
DP  - 1989 Jul
TI  - The antitumor intercalating drug ditercalinium binds preferentially to RNA in 
      Friend erythroleukemia cells.
PG  - 522-9
AB  - Ditercalinium (DIT; NSC 335153), a 7H-pyridocarbazole dimer, was reported to be 
      capable of binding with high affinity to DNA by bisintercalation. Both the 
      cytostatic and cytotoxic effects of this drug have been attributed to its binding 
      to DNA. DIT inhibits the growth and is cytotoxic to Friend erythroleukemia (FL) 
      cells. When FL cells were treated with 0.5-2.5 microM DIT and then stained with 
      acridine orange (AO), which differentially stains DNA and RNA, the green, 
      orthochromatic fluorescence representing AO binding to DNA was unchanged, while 
      the metachromatic red luminescence characteristic of AO binding to RNA was 
      reduced by as much as 40% in 4 hr; the effect was DIT-concentration dependent. 
      The reduction in RNA stainability by DIT in the absence of any significant 
      decrease in RNA content, was also observed with another RNA-specific 
      fluorochrome, pyronin Y (PY). These results indicate that in live cells DIT 
      preferentially binds to RNA rather than DNA, preventing stainability of the 
      former by the monointercalating dyes AO and PY. When FL cells were exposed to 10 
      microM DIT after being first permeabilized by ethanol, the subsequent 
      stainability of DNA in these cells was reduced by up to 67% and RNA by up to 44%, 
      indicating that under these conditions DIT binds to both DNA and RNA. This 
      observation was confirmed by competition experiments between AO and DIT bound to 
      DNA or RNA in permeabilized cells mixed with equivalent numbers of RNA-containing 
      (DNase-treated) or DNA-containing (RNase-treated) cells, respectively. The 
      mechanisms that protect DNA against binding by DIT in live cells are unknown but 
      are lost in fixed cells and may be related to maintenance of cellular and/or 
      nuclear membrane integrity. If the propensity for other intercalating drugs to 
      bind to RNA in live cells is correlated with their antitumor activity as is DIT, 
      the rationale for designing new drugs based solely on their affinity for DNA 
      should be reevaluated.
FAU - Traganos, F
AU  - Traganos F
AD  - Experimental Cell Research Laboratory, Memorial Sloan-Kettering Cancer Center, 
      New York 10021.
FAU - Bueti, C
AU  - Bueti C
FAU - Kapuscinski, J
AU  - Kapuscinski J
FAU - Darzynkiewicz, Z
AU  - Darzynkiewicz Z
LA  - eng
GR  - CA23296/CA/NCI NIH HHS/United States
GR  - CA28704/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Carbazoles)
RN  - 0 (Intercalating Agents)
RN  - 63231-63-0 (RNA)
RN  - 9007-49-2 (DNA)
RN  - F30N4O6XVV (Acridine Orange)
RN  - VFS4ZUK33P (ditercalinium)
RN  - W659G165T1 (Pyronine)
SB  - IM
MH  - Acridine Orange
MH  - Animals
MH  - Antineoplastic Agents/*metabolism
MH  - Binding Sites
MH  - Binding, Competitive
MH  - Carbazoles/*metabolism
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - DNA/metabolism
MH  - Friend murine leukemia virus
MH  - *Intercalating Agents
MH  - Kinetics
MH  - Leukemia, Erythroblastic, Acute/*metabolism
MH  - Luminescent Measurements
MH  - Mice
MH  - Pyronine
MH  - RNA/biosynthesis/*metabolism
MH  - Staining and Labeling
EDAT- 1989/07/01 00:00
MHDA- 1989/07/01 00:01
CRDT- 1989/07/01 00:00
PHST- 1989/07/01 00:00 [pubmed]
PHST- 1989/07/01 00:01 [medline]
PHST- 1989/07/01 00:00 [entrez]
PST - ppublish
SO  - Leukemia. 1989 Jul;3(7):522-9.