Contribution in an anthology

Appeared in: Biothiols Part A Monothiols and Dithiols, Protein Thiols, and Thiyl Radicals

Editor list: Packer, L

Publication year: 1995

Pages: 173-188

ISBN: 0-12-182152-8

eISBN: 978-0-12-182152-4

DOI Link: https://doi.org/10.1016/0076-6879(95)51120-2

Title of series: Methods in Enzymology

Number in series: 251

Abstract: 

This chapter discusses the thiocarbamoylating properties of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU or carmustine). BCNU is a widely used cytostatic drug with activity against brain tumors, lymphomas, leukemia, malignant melanoma, and other neoplasms. In aqueous solution, depending on pH and buffer, BCNU disintegrates slowly into numerous products. The first step of decomposition results in the formation of two electrophilic reactants: the bifunctional alkylating 2-chloroethyl diazohydroxide and the carbamoylating chloroethyl isocyanate. DNA-alkylating and DNA cross-linking derivatives of the diazohydroxide largely mediate the cytostatic effects. Additional mechanisms of BCNU action have been proposed, notably the inhibition of glutathione reductase and the carbamoylation of glutathione (GSH), which yields S-[N-2-(chloroethyl)carbamoyl] glutathione. This compound can be regarded as the carrier of reactive BCNU derivatives. The carbamoylating potential of BCNU contributes both to the desired effects and to the risks of the drug, which include pulmonary fibrosis, bone marrow toxicity, cataract formation, hemolytic crises, and secondary tumors. The chapter discusses the BCNU decomposition product 2-chloroethyl isocyanate, BCNU as inhibitor of glutathione reductase, inhibition of other enzymes by BCNU, revelation of oxidative stress by inhibiting the glutathione redox cycle, and formation and reactions of S-[N-2-(chloroethyl)carbamoyl]-glutathione.

Harvard Citation style: Becker, K. and Schirmer, R. (1995) 1,3-Bis(2-chloroethyl)-1-nitrosourea as a thiol-carbamoylating agent in biological systems, in Packer, L. (ed.) Biothiols Part A Monothiols and Dithiols, Protein Thiols, and Thiyl Radicals. Amsterdam: Academic Press, pp. 173-188. https://doi.org/10.1016/0076-6879(95)51120-2

APA Citation style: Becker, K., & Schirmer, R. (1995). 1,3-Bis(2-chloroethyl)-1-nitrosourea as a thiol-carbamoylating agent in biological systems. In Packer, L. (Ed.), Biothiols Part A Monothiols and Dithiols, Protein Thiols, and Thiyl Radicals (pp. 173-188). Academic Press. https://doi.org/10.1016/0076-6879(95)51120-2