Cytotoxicity of lysomustine and its isomers, and their potential use for selection of cells / Rozov F. N.,Grinenko T. S.,Levit G. L.,Grishakov A. N.,Belyavsky A. V.,Krasnov V. P. // RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY. - 2011. - V. 37, l. 6. - P. 713-718.

ISSN/EISSN:

1068-1620 / нет данных

Type:

Article

Abstract:

N (E >)-Nitroso-N (E >)-{[}N'-(2-chloroethyl)carbamoyl]-L-lysine (I) and N (E >)-{[}N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-lysine (II), the isomers being the constituents of antitumor agent lysomustine, were isolated from the agent by reverse phase HPLC (RP-HPLC). The study of cytotoxicity of the above compounds against K562 cells showed that lesions induced by isomer (II) produce a significant cytotoxic effect, but can be efficiently repaired by the action of MGMT (O6-methylguanine-DNA methyltransferase). Under similar conditions, lesions induced by isomer (I) produce a substantially smaller effect but are weakly, if at all, repairable by MGMT. The effects of a clinically approved agent lysomustine, which is a 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.

Author keywords:

nitrosoureas; lysomustine; isomers; gene therapy; O6-methylguanine-DNA-methyltransferase; O6-benzylguanine VIVO DRUG SELECTION; N-NITROSOUREAS; GENE-THERAPY; STEM-CELLS

DOI:

10.1134/S1068162011060112

Web of Science ID:

ISI:000297344600004

Соавторы в МНС:

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Другие поля

Поле	Значение
Month	NOV
Publisher	MAIK NAUKA/INTERPERIODICA/SPRINGER
Address	233 SPRING ST, NEW YORK, NY 10013-1578 USA
Language	English
Keywords-Plus	VIVO DRUG SELECTION; N-NITROSOUREAS; GENE-THERAPY; STEM-CELLS
Research-Areas	Biochemistry \& Molecular Biology; Chemistry
Web-of-Science-Categories	Biochemistry \& Molecular Biology; Chemistry, Organic
Author-Email	ca@ios.uran.ru
ResearcherID-Numbers	Grinenko, Tatyana/Q-7742-2016
Funding-Acknowledgement	Presidium of the Russian Academy of Sciences; Russian Foundation for Basic Research {[}09-04-01312]; Ural Branch of the Russian Academy of Sciences {[}09-I-3-2004]; Council on Grants at the President of the Russian Federation {[}NSh 65261.2010.3]
Funding-Text	This work was financially supported by the ``Molecular and Cell Biology{''} Program of Basic Research of the Presidium of the Russian Academy of Sciences (for A. V. Belyavsky), the Russian Foundation for Basic Research (Project No. 09-04-01312), the Ural Branch of the Russian Academy of Sciences (Project No. 09-I-3-2004), and the Council on Grants at the President of the Russian Federation (Program of State Support for Leading Scientific Schools of the RF, Grant No. NSh 65261.2010.3).
Number-of-Cited-References	23
Usage-Count-Since-2013	3
Journal-ISO	Russ. J. Bioorg. Chem.
Doc-Delivery-Number	852GL