PMID- 12643770
OWN - NLM
STAT- MEDLINE
DCOM- 20040128
LR  - 20131121
IS  - 0739-1102 (Print)
IS  - 0739-1102 (Linking)
VI  - 20
IP  - 5
DP  - 2003 Apr
TI  - De-intercalation of ethidium bromide and acridine orange by xanthine derivatives 
      and their modulatory effect on anticancer agents: a study of DNA-directed 
      toxicity enlightened by time correlated single photon counting.
PG  - 677-86
AB  - Time Correlated Single Photon Counting (TCSPC) was used for the first time to 
      analyze the effect/changes in the mode of intercalation of ethidium bromide 
      (EtBr) and acridine orange (AO) to calf thymus DNA brought about due to 
      interaction of naturally occurring methylxanthines such as theophylline (X1), 
      theobromine (X2) and caffeine (X3). UV absorption and fluorescence studies were 
      also carried to observe the behaviour of these xanthines on the modulation of the 
      binding mode of anticancer agents (cisplatin, novantrone, and actinomycin D) and 
      certain intercalating dyes (EtBr and AO) to DNA. In TCSPC analysis we found that 
      when the concentration of the drugs (X1, X2 and X3) increased from 0.025 mM to 2 
      mM i.e. P/D 2.4 to P/D 0.03 reduction in intercalation of EtBr and AO was 
      observed, suggesting that xanthine derivatives could play very important role in 
      reducing the DNA-directed toxicity in a dose dependent manner. In TCSPC, the 
      amplitude of smaller lifetime component A(1) and higher lifetime component A(2) 
      are attributed to free and intercalated dye concentration and their variation 
      could indicate the process of intercalation or reduced intercalation of EtBr and 
      AO by xanthine derivatives. We found that at the maximum drug concentration the 
      smaller lifetime component A(1) was increased by 7-8% and 17-37% in EtBr and AO 
      intercalated complex respectively. Also the changes in lifetime and fluorescence 
      decay profile were observed for the DNA-intercalated dyes before and after 
      treatment with xanthines. Especially, at maximum P/D 0.03 the lifetime of 
      DNA-intercalated EtBr and AO reduced by 1-2 ns. The present analysis reveals that 
      xanthines are able to interact with free dyes and also with intercalated dyes, 
      suggesting that when they interact with free dyes they might inhibit the further 
      intercalation of dye molecules to DNA and the interaction with intercalated dyes 
      might lead to displacement of the dyes resulting in de-intercalation. The results 
      obtained from UV and fluorescence spectroscopy also support the present 
      investigation of probable interaction of xanthines with the DNA damaging agents 
      in modulating/reducing the DNA-directed toxicity.
FAU - Johnson, I Maria
AU  - Johnson IM
AD  - Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical 
      Sciences, University of Madras, Taramani, Chennai, 600 113, India.
FAU - Kumar, S G Bhuvan
AU  - Kumar SG
FAU - Malathi, R
AU  - Malathi R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Intercalating Agents)
RN  - 0 (Xanthines)
RN  - 3G6A5W338E (Caffeine)
RN  - 9007-49-2 (DNA)
RN  - 91080-16-9 (calf thymus DNA)
RN  - C137DTR5RG (Theophylline)
RN  - EN464416SI (Ethidium)
RN  - F30N4O6XVV (Acridine Orange)
RN  - OBD445WZ5P (Theobromine)
SB  - IM
MH  - Acridine Orange/*metabolism/toxicity
MH  - Antineoplastic Agents/*metabolism
MH  - Caffeine/pharmacology
MH  - DNA/*metabolism
MH  - Ethidium/*metabolism/toxicity
MH  - Fluorescent Dyes/*metabolism
MH  - Humans
MH  - Intercalating Agents/*metabolism/toxicity
MH  - Models, Biological
MH  - Photons
MH  - Spectrometry, Fluorescence
MH  - Spectrophotometry, Ultraviolet
MH  - Theobromine/pharmacology
MH  - Theophylline/pharmacology
MH  - Xanthines/*pharmacology
EDAT- 2003/03/20 04:00
MHDA- 2004/01/30 05:00
CRDT- 2003/03/20 04:00
PHST- 2003/03/20 04:00 [pubmed]
PHST- 2004/01/30 05:00 [medline]
PHST- 2003/03/20 04:00 [entrez]
AID - d=3013&c=4104&p=11633&do=detail [pii]
AID - 10.1080/07391102.2003.10506884 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2003 Apr;20(5):677-86. doi: 10.1080/07391102.2003.10506884.