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Deoxyribonucleic acid (DNA) is the fundamental molecule that carries genetic instructions for the development, functioning, growth, and reproduction of all known organisms and many viruses [1]. In the context of pharmacology and toxicology, DNA and other cellular macromolecules (including proteins and lipids) serve as primary targets for various cytotoxic agents and reactive metabolites [2]. These drugs interact with DNA through several mechanisms, such as covalent binding (alkylation), non-covalent insertion between base pairs (intercalation), or the induction of single- and double-strand breaks, which collectively inhibit DNA replication and transcription [3]. While these interventions are highly effective at inducing apoptosis in rapidly proliferating malignant cells, their lack of high specificity often results in significant damage to healthy tissues [4]. This non-specific interaction is a hallmark of traditional chemotherapy and underlies many of the severe side effects and long-term risks, such as secondary primary malignancies and organ toxicity, associated with these treatments [2, 4].
Direct chemical modification of DNA through alkylation and cross-linking, physical insertion between base pairs (intercalation), and the induction of oxidative or enzymatic DNA strand breaks [2, 3].
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