PMID- 9918414
OWN - NLM
STAT- MEDLINE
DCOM- 19990419
LR  - 20191024
IS  - 0960-8931 (Print)
IS  - 0960-8931 (Linking)
VI  - 8
IP  - 6
DP  - 1998 Dec
TI  - G2 accumulation and melanin overproduction in malignant melanocytes treated with 
      a new nitrosourea.
PG  - 517-27
AB  - Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea), a 
      new anticancer chloroethylnitrosourea (CENU) is being tested in a phase II 
      clinical trial of disseminated melanoma. The antitumour effect of this drug is 
      mainly due to DNA damage in malignant melanocytes. Recently, we have shown that 
      this damage can induce apoptosis in some melanoma cell lines. In others, 
      apoptosis is not clearly observed, although there is a strong cytostatic effect. 
      In this paper, we have characterized the cytological effect of cystemustine on 
      murine malignant melanocytes (B16 cell line) which are resistant to apoptosis 
      induced by this CENU. The results show that 3 days after cystemustine treatment, 
      these melanocytes had accumulated in phase G2 of the cell cycle. There was then a 
      strong morphological modification during a long cytostatic phase up to 30 days 
      after treatment. During this cytostatic phase, there was uncontrolled DNA 
      synthesis and marked swelling. Also, tyrosinase activity, melanin content and the 
      number of mature melanosomes were greatly increased. These results suggest that 
      when malignant melanocytes are not able to undergo apoptosis after treatment with 
      CENU, they accumulate in G2 and this is followed by enhancement of melanogenesis.
FAU - Buchdahl, C
AU  - Buchdahl C
AD  - INSERM U484, Clermont-Ferrand, France.
FAU - Papon, J
AU  - Papon J
FAU - Communal, Y
AU  - Communal Y
FAU - Bourges, M
AU  - Bourges M
FAU - Madelmont, J C
AU  - Madelmont JC
LA  - eng
PT  - Journal Article
PL  - England
TA  - Melanoma Res
JT  - Melanoma research
JID - 9109623
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Melanins)
RN  - 0 (Nitrosourea Compounds)
RN  - 79955-36-5 (N'-(2-chloroethyl)-N-(2-(methylsulfonyl)ethyl)-N'-nitrosourea)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - *G2 Phase
MH  - Melanins/*biosynthesis
MH  - Melanoma, Experimental/*drug therapy/metabolism/*pathology
MH  - Mice
MH  - Microscopy, Electron
MH  - Monophenol Monooxygenase/metabolism
MH  - Nitrosourea Compounds/*therapeutic use
MH  - Time Factors
MH  - Tumor Cells, Cultured
EDAT- 1999/01/26 00:00
MHDA- 1999/01/26 00:01
CRDT- 1999/01/26 00:00
PHST- 1999/01/26 00:00 [pubmed]
PHST- 1999/01/26 00:01 [medline]
PHST- 1999/01/26 00:00 [entrez]
AID - 10.1097/00008390-199812000-00007 [doi]
PST - ppublish
SO  - Melanoma Res. 1998 Dec;8(6):517-27. doi: 10.1097/00008390-199812000-00007.