Adverse Outcome Pathway on deposition of energy leading to lung cancer
The present Adverse Outcome Pathway (AOP) describes the linkage between lung cancer
initiated from the Deposition of Energy (DoE) into a cell by a prototypic stressor
such as radon gas. The multiple ionization events from DoE can directly break DNA
double strands and initiate the activation of repair machinery through non-homologous
end joining, an efficient, but error-prone process. When double strand breaks occur
in DNA regions that transcribe critical genes, mutations generated by faulty repair
may alter the function of these genes or cause chromosomal aberrations. These events
alter the functions of many gene products and affect cell growth, cycling, and apoptosis.
Cell proliferation is then promoted by escaping the regulatory control and forming
hyperplasia in lung epithelial cells, leading eventually to lung cancer. Although
the weight of evidence for this AOP is strong, uncertainties remain on dose-effect
relationships across KEs, particularly for DoE delivered at low doses and dose-rates.
Published on October 23, 2023
In series:OECD Series on Adverse Outcome Pathwaysview more titles