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How can certain drugs and chemicals cause DNA mutations?
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human genetic disease
Photomicrograph of the BRCA2 tumor suppressor gene on chromosome 13 of the human genome. Inactivation of this growth-regulating gene is associated with a higher risk of developing breast cancer.
Chemicals and drugs induce DNA mutations through complex interactions that modify the genetic material, often rendering it unable to replicate correctly or causing errors during repair. The process frequently involves the metabolism of these substances by the body into reactive intermediates that directly damage DNA.12
Specific mechanisms include:
- Chemical Modification: Agents such as nitrous acid or anions like bisulfite can chemically alter bases, leading to incorrect base pairing. Alkylating agents, often used in chemotherapy, bind to DNA to cause cross-linking between strands or the loss of purine bases, which blocks replication.314
- Oxidative Damage: Many chemicals and drugs generate free radicals or act as oxidizing agents. These create oxidative lesions, such as the oxidation of guanine, which can lead to permanent mutations if not corrected by DNA repair enzymes.315
- Interference with Replication: Some substances act as base analogs or intercalating agents, causing abnormal insertions or deletions in the DNA sequence. Others, such as the drug bleomycin, can induce double-strand breaks.1
Mutations persist when these lesions escape the cell's natural repair mechanisms or when the cell utilizes error-prone repair pathways to bypass the damage.12