Abstract |
Cloretazine [1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl] hydrazine; VNP40101M; 101M] is a relatively new prodrug with activity in elderly acute myelogenous leukemia (AML) patients. Its therapeutic action is due largely to the production of 1-(3-cytosinyl),2-(1-guanyl)ethane cross-links (G-C ethane cross-links) in DNA. The numbers of cross-links produced in three experimental leukemia lines (L1210, U937 and HL-60) were fewer than 10 per genome at their respective LC50 concentrations. Only 1 in approximately 20,000 90CE molecules produces a cross-link in the AGT (O6-alkylguanine-DNA alkyltransferase) negative L1210 and U937 cell lines and 1 in 400,000 in the AGT positive HL-60 cell line.
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Authors | Philip G Penketh, Raymond P Baumann, Kimiko Ishiguro, Krishnamurthy Shyam, Helen A Seow, Alan C Sartorelli |
Journal | Leukemia research
(Leuk Res)
Vol. 32
Issue 10
Pg. 1546-53
(Oct 2008)
ISSN: 0145-2126 [Print] England |
PMID | 18479747
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine
- Antineoplastic Agents
- Cross-Linking Reagents
- Hydrazines
- Sulfonamides
- laromustine
- Guanine
- Cytosine
- DNA
- Ethane
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Topics |
- Animals
- Antineoplastic Agents
(chemistry, therapeutic use, toxicity)
- Cell Line, Tumor
- Cross-Linking Reagents
(chemistry, toxicity)
- Cytosine
(chemistry)
- DNA
(chemistry)
- Ethane
(chemistry)
- Guanine
(chemistry)
- HL-60 Cells
- Humans
- Hydrazines
(chemistry, therapeutic use, toxicity)
- Leukemia
(drug therapy)
- Mice
- Sulfonamides
(chemistry, therapeutic use, toxicity)
- U937 Cells
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