Clastogenesis

Clastogenesis is the process by which chromosomal fragments are produced in a cell as a result of DNA damage, particularly strand breaks caused by clastogenic agents. In cytogenetics, clastogenesis refers to the creation of chromosomal breakages and subsequent structural rearrangements that can be inherited by progeny cells during cell division.

The primary initiating event is a double-strand break in DNA. If breaks are misrepaired, structural chromosomal aberrations arise, such as deletions, duplications, inversions, translocations, and the formation of acentric or dicentric fragments. Repair pathways include non-homologous end joining and homologous recombination; errors in these pathways lead to clastogenic outcomes.

Clastogenic agents include physical factors such as ionizing radiation; chemical agents including alkylating agents, intercalating agents, polycyclic aromatic hydrocarbons, and some metals; reactive oxygen species; and certain anticancer drugs. Replication stress and telomere dysfunction can also promote clastogenesis.

In toxicology and medicine, clastogenesis is assessed by cytogenetic assays that detect chromosomal breaks and rearrangements, such as chromosome aberration tests and micronucleus assays. These tests help evaluate potential carcinogenic risk and the safety of chemicals and drugs. Clastogenic effects are distinguished from aneugenic effects, which perturb chromosome number rather than structure.

Over time, clastogenesis contributes to genomic instability and may be involved in cancer development and congenital abnormalities when occurring in germ cells or during development.