PMID- 17382605
OWN - NLM
STAT- MEDLINE
DCOM- 20071025
LR  - 20081121
IS  - 1568-7864 (Print)
IS  - 1568-7856 (Linking)
VI  - 6
IP  - 9
DP  - 2007 Sep 1
TI  - Change in expression of MGMT during maturation of human monocytes into dendritic 
      cells.
PG  - 1255-63
AB  - Dendritic cells (DCs) maturated from monocytes play an important role in the 
      immune system, not only in defense against conventional infections but also in 
      cancer rejection. Because of the central role of DCs in tumor host defense it is 
      highly important that DCs as well as the progenitor cell population are protected 
      during cancer therapy. Since most anticancer drugs target DNA, the DNA repair 
      capacity is most importance for the response of DCs and their precursor cells. 
      Here, we studied the expression of the DNA repair protein O6-methylguanine-DNA 
      methyltransferase (MGMT) in monocytes obtained from peripheral blood of healthy 
      donors and DCs maturated from monocytes (moDCs). We show that MGMT is expressed 
      at high level in monocytes, comparable to peripheral lymphocytes. The MGMT 
      expression level declines, however, during DC maturation reaching the low level 
      of CD34+ haematopoetic stem cells. Decline of MGMT was observed on activity, 
      protein and RNA level. It is not related to MGMT promoter methylation, suggesting 
      silencing of the MGMT gene in moDCs occurs by other means. Since maturation of 
      monocytes into DCs is provoked by IL-4 and GM-CSF, the data indicate that MGMT is 
      subject to cytokine-mediated regulation. Despite of the high MGMT level, 
      monocytes were more sensitive to methylating agents (MNNG, temozolomide) and 
      equally sensitive to the chloroethylating agent fotemustine than moDCs, 
      undergoing apoptosis upon treatment. The data provide an example that high MGMT 
      expression level does not necessarily implicate a higher level of resistance 
      against O6-alkylating agents.
FAU - Briegert, Manuela
AU  - Briegert M
AD  - Institute of Toxicology, University of Mainz, Obere Zahlbacher Str. 67, D-55131 
      Mainz, Germany.
FAU - Enk, Alexander H
AU  - Enk AH
FAU - Kaina, Bernd
AU  - Kaina B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070326
PL  - Netherlands
TA  - DNA Repair (Amst)
JT  - DNA repair
JID - 101139138
RN  - 0 (Alkylating Agents)
RN  - 0 (Antigens, CD34)
RN  - 0 (Cytokines)
RN  - EC 2.1.1.63 (O(6)-Methylguanine-DNA Methyltransferase)
SB  - IM
MH  - Alkylating Agents/pharmacology
MH  - Antigens, CD34/metabolism
MH  - Apoptosis/drug effects
MH  - Cell Differentiation/*physiology
MH  - Cells, Cultured
MH  - Cytokines/pharmacology
MH  - DNA Methylation/drug effects
MH  - DNA Repair
MH  - Dendritic Cells/*cytology/enzymology/immunology
MH  - Flow Cytometry
MH  - Humans
MH  - Lymphocytes/cytology/metabolism
MH  - Monocytes/*cytology/enzymology/immunology
MH  - O(6)-Methylguanine-DNA Methyltransferase/*metabolism
MH  - Promoter Regions, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2007/03/27 09:00
MHDA- 2007/10/27 09:00
CRDT- 2007/03/27 09:00
PHST- 2005/09/22 00:00 [received]
PHST- 2007/02/03 00:00 [revised]
PHST- 2007/02/07 00:00 [accepted]
PHST- 2007/03/27 09:00 [pubmed]
PHST- 2007/10/27 09:00 [medline]
PHST- 2007/03/27 09:00 [entrez]
AID - S1568-7864(07)00062-6 [pii]
AID - 10.1016/j.dnarep.2007.02.008 [doi]
PST - ppublish
SO  - DNA Repair (Amst). 2007 Sep 1;6(9):1255-63. doi: 10.1016/j.dnarep.2007.02.008. 
      Epub 2007 Mar 26.