Genotoxins

Genotoxins are substances or factors that damage the genetic material in cells, including DNA and RNA. They can induce mutations, chromosomal aberrations, and other heritable alterations, and are linked to cancer, teratogenic effects, and reproductive toxicity. Genotoxic effects may result from direct interaction with DNA, indirect damage through reactive species, or interference with DNA replication or repair.

Common sources include chemical agents such as alkylating agents, nitrosamines, polycyclic aromatic hydrocarbons, heavy metals, aflatoxins; physical agents such as ionizing and ultraviolet radiation; and some biological agents. Endogenous processes like reactive oxygen species also contribute. Damage types include DNA adduct formation, base modifications, single- and double-strand breaks, cross-links, and replication fork stalling.

Health impact depends on dose, duration, and repair capacity. Genotoxicity testing informs risk assessment and regulatory decisions; genotoxic carcinogens are frequently assumed to have no safe threshold in human health risk assessment, though context matters. Long-term exposure increases cancer risk and can cause heritable genetic changes.

In medicine, genotoxic agents are used as chemotherapy and radiotherapy, exploiting DNA damage to kill cancer cells, but they pose risks to patients and workers. Examples include alkylating agents (cyclophosphamide), platinum compounds (cisplatin), vinyl chloride, benzene, formaldehyde, and aflatoxins.

Assessment and detection rely on assays such as the comet assay, micronucleus test, and the Ames test, as well as newer genomic approaches. Cells repair genotoxic lesions via base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair pathways. Protective measures reduce exposure in occupational and environmental settings.