title: [Cytotoxicity of lysomustine and its isomers, and their potential use for selection of cells].
abstract: N epsilon-Nitroso-N epsilon- [N'-(2-chloroethyl)carbamoyl]-L-lysine (I) and N epsilon- [N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-lysine (II), the isomers being the constituents of antitumor agent Lysomustine, were obtained by RFHPLC. The study of cytotoxicity of the above compounds against K562 cells showed that the lesions induced by isomer (II) produce a significant cytotoxic effect but can be efficiently repaired by the action of MGMT (O6-methylaguanine DNA methyltransferase). Under similar conditions, the lesions induced by isomer (I) produce substantially smaller effect but are weakly if at all repairable by MGMT. The effects of a clinically approved agent Lysomustine, which is the mixture of isomers (I) and (II), are similar to those of isomer (II). The results obtained point to a different chemical nature of DNA lesions induced by two Lysomustine isomers. Our data indicate that Lysomustine and its isomer (II) can be used for in vitro selection of cells expressing MGMT.
authors.forename: F N
authors.initials: FN
authors.lastname: Rozov
authors.forename: T S
authors.initials: TS
authors.lastname: Grinenko
authors.forename: G L
authors.initials: GL
authors.lastname: Levit
authors.forename: A N
authors.initials: AN
authors.lastname: Grishakov
authors.forename: A V
authors.initials: AV
authors.lastname: Beliavskiĭ
authors.forename: V P
authors.initials: VP
authors.lastname: Krasnov
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D009607:Nitrosourea Compounds / Q000737:chemistry / Q000494:pharmacology*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism*; D020011:Protective Agents / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D020011:Protective Agents; D020033:Protein Isoforms; C552857:lysomustine; D019853:O(6)-Methylguanine-DNA Methyltransferase