N7-guanine DNA adduct

N7-guanine DNA adducts refer to chemical modifications occurring at the N7 nitrogen atom of the guanine base in DNA. This position acts as a nucleophilic site for alkylating agents (chemicals or drugs), leading to the formation of various N7-alkylguanine or N7-platinated guanine lesions. These adducts are the most common initial sites of DNA alkylation and platination. While not directly miscoding, the lesions are chemically unstable, and their depurination can result in apurinic (AP) sites, mutagenesis, and strand breaks. Formation and persistence of N7-guanine adducts are implicated in the genotoxic and cytotoxic effects of many anti-cancer drugs (e.g., cisplatin) as well as in environmental carcinogenesis. Quantification of such adducts serves as a measure of exposure to certain mutagenic agents. However, their unstable nature limits their utility as robust biomarkers in broad clinical practice.

Other names

N7-guanine adductN7-alkylguanine (for alkylated species)N7-(2-hydroxypropyl)guanine (example of a specific adduct)N7-platinated guanine (for cisplatin and related adducts)N7-GuaN7-GuanineN7-G

Drugs such as cisplatin form covalent bonds with the N7 position of guanine in DNA, leading to intra- and interstrand crosslinks, DNA helix distortion, and inhibition of replication and transcription, resulting in cytotoxicity and apoptosis in rapidly dividing cells. Alkylating agents transfer alkyl groups to N7 of guanine, leading to DNA instability, depurination, mispairing, or strand breaks.