PMID- 7840782
OWN - NLM
STAT- MEDLINE
DCOM- 19950224
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 49
IP  - 1
DP  - 1995 Jan 6
TI  - Reversal of methylmercaptopurine ribonucleoside cytotoxicity by purine 
      ribonucleosides and adenine.
PG  - 49-56
AB  - 6-Methylmercaptopurine ribonucleoside-5'-phosphate (MeSPuRMP), the sole 
      metabolite of 6-methylmercaptopurine ribonucleoside (MeSPuRib), is a strong 
      inhibitor of purine de novo synthesis, inducing depletion of intracellular purine 
      nucleotides and subsequent cell death in several tumor cell lines. In this study 
      prevention of MeSPuRib cytotoxicity by compounds of the purine salvage pathway 
      was studied in Molt F4 human malignant T-lymphoblasts. Adenosine, adenine and 
      inosine were able to prevent depletion of the adenine nucleotide pool when used 
      in combination with 0.5 microM MeSPuRib, but had virtually no effect on depletion 
      of guanine nucleotides. Nevertheless, these three purine compounds were able to 
      reduce the cytotoxic effects induced by MeSPuRib. Addition of guanosine to cells 
      treated with 0.5 microM MeSPuRib normalized the guanine nucleotide pool, but 
      adenine nucleotides remained depleted. Under these conditions, inhibition of cell 
      growth was significantly decreased. With the combination of guanosine and 10 
      microM MeSPuRib, cytotoxicity was increased compared to 10 microM MeSPuRib alone, 
      associated with a depletion of adenine nucleotides to 9% of untreated cells. 
      Since cell growth and cell viability of Molt F4 cells are less inhibited by 
      MeSPuRib under conditions where adenine nucleotide depletion is prevented by 
      purine compounds (and where the other nucleotides are depleted) we conclude that 
      depletion of adenine nucleotides is an important factor in MeSPuRib cytotoxicity.
FAU - Stet, E H
AU  - Stet EH
AD  - Department of Pediatrics, St Radboud University Hospital of Nijmegen, The 
      Netherlands.
FAU - De Abreu, R A
AU  - De Abreu RA
FAU - Bokkerink, J P
AU  - Bokkerink JP
FAU - Lambooy, L H
AU  - Lambooy LH
FAU - Vogels-Mentink, T M
AU  - Vogels-Mentink TM
FAU - Keizer-Garritsen, J J
AU  - Keizer-Garritsen JJ
FAU - Trijbels, F J
AU  - Trijbels FJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Nucleosides)
RN  - 0 (Nucleotides)
RN  - 0 (Purine Nucleosides)
RN  - 0 (Ribonucleosides)
RN  - 0 (Thionucleotides)
RN  - 12133JR80S (Guanosine)
RN  - 342-69-8 (Methylthioinosine)
RN  - 46S541971T (Thioinosine)
RN  - 5A614L51CT (Inosine)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - 7021-52-5 (6-methylthiopurine ribonucleoside-5'-phosphate)
RN  - E7WED276I5 (Mercaptopurine)
RN  - JAC85A2161 (Adenine)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenine/*pharmacology
MH  - Adenosine/pharmacology
MH  - Antineoplastic Agents/toxicity
MH  - Cell Division/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Guanosine/pharmacology
MH  - Humans
MH  - Inosine/pharmacology
MH  - Mercaptopurine/*analogs & derivatives/antagonists & inhibitors/toxicity
MH  - Methylthioinosine/*antagonists & inhibitors/*toxicity
MH  - Nucleosides/metabolism
MH  - Nucleotides/metabolism
MH  - Purine Nucleosides/*pharmacology
MH  - Ribonucleosides/*antagonists & inhibitors/*toxicity
MH  - T-Lymphocytes/cytology/drug effects
MH  - Thioinosine/analogs & derivatives/toxicity
MH  - Thionucleotides/toxicity
EDAT- 1995/01/06 00:00
MHDA- 1995/01/06 00:01
CRDT- 1995/01/06 00:00
PHST- 1995/01/06 00:00 [pubmed]
PHST- 1995/01/06 00:01 [medline]
PHST- 1995/01/06 00:00 [entrez]
AID - 0006295294003872 [pii]
AID - 10.1016/0006-2952(94)00387-2 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1995 Jan 6;49(1):49-56. doi: 10.1016/0006-2952(94)00387-2.