genotoxic

Genotoxic refers to substances or agents that damage DNA or chromosomes, leading to mutations, chromosomal alterations, or dysregulated gene expression. Genotoxic effects can contribute to carcinogenesis and heritable changes.

Genotoxicity can arise from direct interaction with genetic material or indirectly through metabolic activation and reactive intermediates. Direct mechanisms include formation of DNA adducts, crosslinks (inter- and intra-strand), strand breaks, and base modifications. Indirect mechanisms involve reactive oxygen species generated by metabolism or interference with DNA replication; some agents also disrupt mitosis and chromosome segregation, contributing to genomic instability.

Examples of genotoxic agents include chemicals such as alkylating agents (nitrogen mustards, platinum compounds), polycyclic aromatic hydrocarbons, and aflatoxin B1; physical agents such as ultraviolet light and ionizing radiation; and certain metals like chromium(VI) and arsenic. Environmental and occupational exposures to these agents are routinely assessed for genotoxic potential.

Genotoxicity can be assessed with a range of tests, including the Ames bacterial reverse mutation assay, micronucleus assays, chromosomal aberration tests, and the comet assay, in vitro and in vivo. These assays support risk assessment and regulatory decisions in pharmaceuticals, chemicals, and environmental health.

Repair of genotoxic damage is accomplished by cellular DNA repair pathways such as base excision repair, nucleotide excision repair, homologous recombination, and non-homologous end joining. When repair is incomplete or erroneous, mutations or chromosomal alterations can arise, linking genotoxic exposure to cancer and hereditary genetic effects.