ABSTRACT
Interstrand cross-links (ICLs) that covalently bond two complementary strands of the Watson-Crick DNA double helix represent a dangerous cytotoxic form of DNA damage that effectively blocks the vital cellular processes of DNA replication and transcription (Deans and West 2011). Although DNA ICLs are well known to be induced by certain chemical agents, such as cisplatin and mitomycin C (MMC) that are conventionally used as chemotherapy drugs, it is more controversial as to the extent of naturally occurring ICLs and if these endogenous forms cause cancer or other diseases. The most prominent natural source of ICLs arise from lipid peroxidation products, such as malondialdehyde (Kozekov et al. 2003; Stone et al. 2008); however, similar to the situation for ICL-inducing agents, it is yet unclear if other forms of DNA damage, such as monoadducts, contribute to the cytotoxicity and phenotypes, such as cancer or age-related symptoms, that are associated with a cross-link repair defi ciency (Deans and West 2011).
