PMID- 7967706
OWN - NLM
STAT- MEDLINE
DCOM- 19941216
LR  - 20190825
IS  - 0145-2126 (Print)
IS  - 0145-2126 (Linking)
VI  - 18
IP  - 11
DP  - 1994 Nov
TI  - The cytotoxicity of thioguanine vs mercaptopurine in acute lymphoblastic 
      leukemia.
PG  - 805-10
AB  - The use of mercaptopurine (MP) rather than thioguanine (TG) in the treatment of 
      childhood acute lymphoblastic leukemia (ALL) has occurred for historical reasons, 
      but does not have a pharmacologic basis. The purpose of this study was to begin 
      to address whether TG would be more efficacious than MP in the treatment of 
      childhood ALL. Preclinical cytotoxicity studies were performed using human 
      leukemic cell lines and leukemic cells from patients with ALL. First, the 
      concentration-survival curves for MP and TG in three human leukemic cell lines 
      (MOLT-4, CCRF-CEM and Wilson) were determined. The second group of experiments 
      determined the concentration-time dependence for cytotoxicity of MP and TG. The 
      final group of experiments compared the in vitro cytotoxicity of MP to TG in 
      leukemic cells from patients with ALL. The thiopurines displayed classical 
      anti-metabolite cytotoxicity profiles, exhibiting a cytotoxicity threshold 
      concentration and demonstrating an increase in cell kill with prolongation of 
      exposure to the drug. For MP, the cytotoxicity threshold was approximately 1 
      microM, with maximum cytotoxicity occurring with 10 microM concentrations. For 
      TG, the threshold was only 0.05 microM with maximum cytotoxicity occurring at 0.5 
      microM. Exposure to MP for more than 8 h was necessary to produce cytotoxicity, 
      whereas exposures as short as 4 h were required for TG. Leukemic cells from 
      children with ALL were also more sensitive to TG than to MP. The median IC50 for 
      TG (20 microM) was significantly lower than that for MP (> or = 206 microM). The 
      data presented here provide a strong rationale for evaluating TG in place of MP 
      in the treatment of childhood ALL. The more direct intracellular activation 
      pathway, higher potency, and shorter duration of drug exposure necessary for 
      cytotoxicity all suggest that TG may have an advantage over MP.
FAU - Adamson, P C
AU  - Adamson PC
AD  - Pharmacology and Experimental Therapeutics Section, National Cancer Institute, 
      Bethesda, Maryland 20892.
FAU - Poplack, D G
AU  - Poplack DG
FAU - Balis, F M
AU  - Balis FM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
SB  - IM
CIN - Leuk Res. 1994 Nov;18(11):811-4. PMID: 7967707
MH  - Adolescent
MH  - Adult
MH  - Cell Survival/drug effects
MH  - Child
MH  - Child, Preschool
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Mercaptopurine/*pharmacology
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*pathology
MH  - Thioguanine/*pharmacology
MH  - Time Factors
MH  - Tumor Cells, Cultured/drug effects/pathology
EDAT- 1994/11/01 00:00
MHDA- 1994/11/01 00:01
CRDT- 1994/11/01 00:00
PHST- 1994/11/01 00:00 [pubmed]
PHST- 1994/11/01 00:01 [medline]
PHST- 1994/11/01 00:00 [entrez]
AID - 0145-2126(94)90159-7 [pii]
AID - 10.1016/0145-2126(94)90159-7 [doi]
PST - ppublish
SO  - Leuk Res. 1994 Nov;18(11):805-10. doi: 10.1016/0145-2126(94)90159-7.