Abstract
Alkylating agents are a series of potentially carcinogenic compounds that are able to introduce lesions into deoxyribonucleic acid (DNA; ref. 1). For their electrophilic nature, alkylating agents have an affinity for the nucleophilic centers of DNA and are monofunctional (have one reactive group) or bifunctional (have two reactive groups). Alkylating agents, such as methylmethanesulphonate and N-ethyl-N-nitrosourea, introduce methyl, ethyl, and complicated alkyl groups to the functional groups of nucleic acid bases, with ring nitrogens being generally more reactive than ring oxygens (2–4). The alkylation of oxygen in phosphodiester bonds results in phosphotriester formation (5) and bifunctional agents often react with two nucleophilic centers, producing inter- and intrastrand crosslinks (6).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Lawley, P. D. (1989) Mutagens as carcinogens: development of current concept. Mutat. Res. 213, 3–25.
Lawley, P. D. (1966) Effects of some chemical mutagens and carcinogens on nucleic acid. Prog. Nucleic Acid Res. Mol. Biol. 5, 89–131.
Loveless, A. (1966) Genetic and Allied Effects of Alkylating Agents. Butterworths, London.
Roberts, J. J. (1978) The repair of DNA modified by cytotoxic, mutagenic, and carcinogenic chemicals. Adv. Radiat. Biol. 7, 211–435.
Singer, B. (1986) O-Alkyl pyrimidines in mutagenesis and carcinogenesis: occurrence and significance. Cancer Res. 46, 4879–4885
Friedberg, E. C., Walker, G. C., and Siede, W. (1995) DNA Repair and Mutagenesis. ASM Press, Washington.
Schendel, P. F. and P. E. Robins. (1978) Repair of O6-methylguanine in adapted Escherichia coli. Proc. Natl. Acad. Sci. USA 75, 6017–6020.
Boulden, A. M., Foote, R. S., Fleming, G. S., and Mitra, S. (1987) Purification and some properties of human O6-methylguanine methyltransferase. J. Biosci. 11, 215–224.
Tronov V. A., Konstantinov E. M., and Kramarenko I. I. (2002) Role of excision mechanisms of DNA repair in induction of apoptosis. Biochemistry (Mosc) 67, 730–736.
Bernstein C., Bernstein H., Payne C. M., and Garewal H. (2002) DNA repair/proapoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat. Res. 511, 145–178.
Bellacosa, A. (2001) Functional interactions and signaling properties of mammalian DNA mismatch repair proteins. Cell Death Differ. 8, 1076–1092.
Margison G. P., Santibanez Koref, M. F., and Povey A. C. (2002) Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine. Mutagenesis 17, 483–487.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Humana Press Inc.
About this protocol
Cite this protocol
Cortellino, S., Turner, D.P., Albino, D., Bellacosa, A. (2004). Induction of Deoxyribonucleic Acid Damage by Alkylating Agents. In: Giordano, A., Romano, G. (eds) Cell Cycle Control and Dysregulation Protocols. Methods in Molecular Biology™, vol 285. Humana Press. https://doi.org/10.1385/1-59259-822-6:121
Download citation
DOI: https://doi.org/10.1385/1-59259-822-6:121
Publisher Name: Humana Press
Print ISBN: 978-0-89603-949-0
Online ISBN: 978-1-59259-822-9
eBook Packages: Springer Protocols