PMID- 3297306
OWN - NLM
STAT- MEDLINE
DCOM- 19870820
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 47
IP  - 14
DP  - 1987 Jul 15
TI  - Effect of adenosine analogues on protein carboxylmethyltransferase, 
      S-adenosylhomocysteine hydrolase, and ribonucleotide reductase activity in murine 
      neuroblastoma cells.
PG  - 3656-61
AB  - The noncompetitive S-adenosylhomocysteine (AdoHcy) hydrolase antagonist adenosine 
      dialdehyde (AD) has been shown to suppress the growth of cultured C-1300 murine 
      neuroblastoma (MNB) cells. The enzymatic sites at which AD and other nucleoside 
      analogues exert their cytotoxic effects have been postulated to include protein 
      carboxylmethyltransferase (PCM), AdoHcy hydrolase, and ribonucleotide reductase. 
      AD (10(-5) M) increased PCM activity 350% in suspensions prepared from disrupted 
      cells after 72 h of drug exposure; in contrast, 3-deazaadenosine (10(-4) M) 
      increased PCM activity 57%, whereas AdoHcy and sinefungin had no effect. When 
      intact MNB cells were incubated with AD for varying time periods up to 72 h and 
      then pulse labeled with the S-adenosylmethionine precursor L-[3H]-methionine, AD 
      (10(-8) to 5 X 10(-6) M) produced a concentration-dependent inhibition of protein 
      carboxylmethylation which persisted for up to 6 h. Following extended periods of 
      AD treatment (48 to 72 h), AD (10(-6) to 10(-5) M) produced a 250% increment in 
      protein carboxylmethylation, similar in magnitude to that observed in disrupted 
      cell preparations. This increase in carboxylmethylation was observed at 
      timepoints when AdoHcy hydrolase activity remained suppressed. The inhibitory 
      effect of AD on AdoHcy hydrolase activity was maximal within 4 h and still 
      apparent after 72 h of incubation. In contrast, AD treatment had no effect on the 
      ribonucleotide reductase activity of MNB cells. These data suggest that the 
      cytotoxic effect of AD on MNB cells results directly from its inhibition of 
      AdoHcy hydrolase activity and indirectly through its suppression of 
      methyltransferase enzyme systems. The potential linkage between the observed 
      long-term elevations in PCM activity and AD-induced cytotoxicity remains to be 
      defined.
FAU - O'Dea, R F
AU  - O'Dea RF
FAU - Mirkin, B L
AU  - Mirkin BL
FAU - Hogenkamp, H P
AU  - Hogenkamp HP
FAU - Barten, D M
AU  - Barten DM
LA  - eng
GR  - GM33776/GM/NIGMS NIH HHS/United States
GR  - NS-17194/NS/NINDS NIH HHS/United States
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  - 34240-05-6 (periodate-oxidized adenosine)
RN  - 979-92-0 (S-Adenosylhomocysteine)
RN  - EC 1.17.4.- (Ribonucleotide Reductases)
RN  - EC 2.1.1.- (Protein Methyltransferases)
RN  - EC 2.1.1.- (Protein O-Methyltransferase)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.3.1.1 (Adenosylhomocysteinase)
RN  - K72T3FS567 (Adenosine)
RN  - M351LCX45Y (Tubercidin)
RN  - W2U467CIIL (sinefungin)
SB  - IM
MH  - Adenosine/*analogs & derivatives/pharmacology
MH  - Adenosylhomocysteinase
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Hydrolases/*metabolism
MH  - Mice
MH  - Neuroblastoma/*enzymology
MH  - Protein Methyltransferases/*metabolism
MH  - Protein O-Methyltransferase/*metabolism
MH  - Ribonucleotide Reductases/*metabolism
MH  - S-Adenosylhomocysteine/pharmacology
MH  - Tubercidin/pharmacology
EDAT- 1987/07/15 00:00
MHDA- 1987/07/15 00:01
CRDT- 1987/07/15 00:00
PHST- 1987/07/15 00:00 [pubmed]
PHST- 1987/07/15 00:01 [medline]
PHST- 1987/07/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1987 Jul 15;47(14):3656-61.