PMID- 1742729
OWN - NLM
STAT- MEDLINE
DCOM- 19920115
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 51
IP  - 24
DP  - 1991 Dec 15
TI  - Measurement of serum L-asparagine in the presence of L-asparaginase requires the 
      presence of an L-asparaginase inhibitor.
PG  - 6568-73
AB  - The antileukemic activity of L-asparaginase (ASNase), an important component of 
      therapy for acute lymphoblastic leukemia, is thought to result from depletion of 
      serum L-asparagine (Asn). In studies of the pharmacological effects of ASNase, 
      investigators have reported prolonged reduction in the serum concentration of Asn 
      after the administration of ASNase. Such measurements may not be valid because 
      ASNase present in the blood sample may hydrolyze Asn before its determination. We 
      examined recovery of [U-14C]Asn from blood samples with and without various 
      concentrations of added ASNase. In the presence of greater than or equal to 0.01 
      IU/ml of ASNase, the amount of [U-14C]Asn recovered was less than 15% of that 
      without ASNase. Utilizing this assay, we studied the effect of 2 known inhibitors 
      of ASNase in an attempt to improve Asn recovery. In the presence of aspartic beta 
      semialdehyde (ASA), or 5-diazo-4-oxo-L-norvaline (DONV), and up to 1.0 IU/ml 
      ASNase, Asn levels remained at greater than 90% of control. ASA prevented the 
      hydrolysis of exogenous Asn in blood samples drawn from patients after ASNase 
      injection. We also developed a method to determine Asn in serum utilizing high 
      pressure liquid chromatography. Using this method, we found that the Asn level 
      was greater than 90% of a normal level in the presence of 40 mM DONV and 1.0 
      IU/ml ASNase. Examination of serum from 4 patients treated with ASNase showed 
      that Asn is detectable 7-19 days sooner when DONV is present in the blood 
      collection system than in its absence. We conclude that: (a) as little as 0.01 
      IU/ml ASNase can hydrolyze Asn added to blood; (b) continued hydrolysis of Asn by 
      ASNase ex vivo can result in falsely low serum Asn measurements; (c) ASA or DONV 
      present in the collection tubes obviates the problem of continued ASNase 
      activity; and (d) the degree and duration of Asn depletion after ASNase therapy 
      is much less than previously believed. Thus, for accurate measurements of the 
      duration and degree of Asn depletion by ASNase, an ASNase inhibitor such as ASA 
      or DONV should be present in the blood collection system.
FAU - Asselin, B L
AU  - Asselin BL
AD  - Strong Children's Research Center, University of Rochester, New York 14642.
FAU - Lorenson, M Y
AU  - Lorenson MY
FAU - Whitin, J C
AU  - Whitin JC
FAU - Coppola, D J
AU  - Coppola DJ
FAU - Kende, A S
AU  - Kende AS
FAU - Blakley, R L
AU  - Blakley RL
FAU - Cohen, H J
AU  - Cohen HJ
LA  - eng
GR  - 00199-03/PHS HHS/United States
GR  - 5P01CA34183-06/CA/NCI NIH HHS/United States
GR  - RR-0044/RR/NCRR NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 17808-06-9 (5-diazo-4-oxonorvaline)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 498-20-4 (aspartic semialdehyde)
RN  - 7006-34-0 (Asparagine)
RN  - 88755TAZ87 (Aminolevulinic Acid)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Aminolevulinic Acid/analogs & derivatives/pharmacology
MH  - Asparaginase/*antagonists & inhibitors/pharmacology/therapeutic use
MH  - Asparagine/*blood
MH  - Aspartic Acid/analogs & derivatives/blood/pharmacology/therapeutic use
MH  - Chromatography, High Pressure Liquid
MH  - Humans
EDAT- 1991/12/15 00:00
MHDA- 1991/12/15 00:01
CRDT- 1991/12/15 00:00
PHST- 1991/12/15 00:00 [pubmed]
PHST- 1991/12/15 00:01 [medline]
PHST- 1991/12/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1991 Dec 15;51(24):6568-73.