Oncogenicity

Oncogenicity is the property of a substance, agent, or exposure that has the potential to cause cancer by promoting the development of tumors in living organisms. It is distinguished from oncogenesis, the biological process by which normal cells become cancerous, typically involving initiation, promotion, and progression of neoplastic growth. Oncogenicity is assessed in experimental models to inform risk assessment and regulatory decisions.

Mechanisms include genetic changes such as activation of oncogenes (for example, RAS or MYC) and inactivation of tumor suppressors (TP53, RB), as well as chromosomal translocations, DNA damage and genomic instability. Epigenetic alterations and altered microRNA expression, and dysregulation of signaling pathways such as MAPK and PI3K/AKT/mTOR, contribute to oncogenicity. Viral genes that transform cells or external agents that create a conducive environment for clonal expansion also play a role.

Examples span viral oncogenicity (human papillomavirus expresses E6 and E7 proteins that disrupt p53 and RB), hepatitis B and C viruses in liver cancer, Epstein–Barr virus, and human T-lymphotropic virus 1; chemical carcinogens such as aflatoxin B1, polycyclic aromatic hydrocarbons, nitrosamines; physical agents such as ionizing and ultraviolet radiation. Lifestyle factors that increase exposure can influence risk.

Assessment methods include in vitro transformation assays (focus formation, soft agar), and in vivo tumorigenicity tests in rodents or other models. Regulatory agencies such as the International Agency for Research on Cancer (IARC), the National Toxicology Program, and other national bodies synthesize oncogenicity information for risk classification. Limitations include species differences, dose relevance, and the context of exposure, which can affect extrapolation to humans.