Alkylating agents can be defined as compounds capable of covalently attaching an alkyl group to a biomolecule under physiological conditions (aqueous solution, 37°C, pH7.4).
Alkylating agents are electrophiles that can covalently bind to nucleophilic sites on cellular macromolecules, including DNA, to form adducts. Alkylating agents comprise a diverse group of chemical compounds, and sources include industrial chemicals, environmental contaminants, naturally occurring compounds, chemotherapeutic drugs, and experimental carcinogens. In addition to these exogenous sources, there is strong evidence that DNA alkylating species are also produced endogenously. Interest in alkylating agents derives, in large part, from findings that many of these compounds are mutagenic or carcinogenic.
DNA alkylation is a characteristic common to many carcinogens. Some carcinogens are not inherently reactive, but are metabolically activated to DNA reactive intermediates. Initiation of carcinogenesis involves chemical modification of DNA, followed by replication to convert a repairable lesion into a heritable mutation (Balmain and Brown 1988; Harris 1991; Saffhill et al. 1985; Swenberg et al. 1990; Weinberg 1989). Mutations that occur at critical sequences in DNA can lead to activation of oncogenes and inactivation of tumor suppressor genes, which can lead to the initiation and progression of cancer