Abstract
Experiments using various test systems have demonstrated that agents with carcinogenic potential are also mutagenic in both prokaryotic and eukaryotic systems (Ames, 1979; Moore et al., 1988; Yuspa et al., 1989). Model studies using experimental animals and cultured cells associate the initiation step in the process of multistage carcinogenesis, with the structural alterations of the cellular DNA (Harris and Autrup, 1983; Cairns, 1981). The modifications of DNA structure can ultimately lead to abnormal cellular function unless the induced damage is repaired prior to the commencement of the cellular DNA replication. DNA alkylating agents e.g., nitrosoureas or nitrosoguanidines are a class of chemical compounds that mediate their biological effects through interactions with nucleophilic sites in DNA and formation of alkyl adducts. The chemistry and extent of formation of these adducts as well as their subsequent fate in the living cell plays a critical role in the mutagenic and carcinogenic processes (Margison and O’Connor, 1979; O’Connor et al., 1979). Elucidation of the mechanism(s), by which a variety of different adducts elicit changes in cellular phenotype, has been an area of intense pathobiological investigation. In-depth studies have been performed on the chemistry and reactivity of different alkylation agents.