Carcinogenesis: Chemicals And Radiation

Chemicals

• Extremely diverse structure, including natural and synthetic products

• Can be direct acting that require no chemical transformation and are usually weak carcinogens; or procarcinogens, that act indirectly by being activated by promoters that augment their carcinogenicity and turn them into the active unlimate carcinogens.

• Promoters by themselves have little, if any, transforming power

• All direct-reacting and ultimate chemical carcinogens are highly reactive electrophiles that react with electron rich atoms in RNA, cellular proteins, and mainly DNA

• Chemical carcinogens usually target the RAS gene as well as the TP53 tumor suppressor genes.

Radiation

• Ionizing radiation can cause chromosome breakage, translocations, and less frequently point mutations. The most important cause for carcinogenesis is the breakage of double stranded DNA.

• The latent period of radiation-associated cancers is very long and the cancer emerges only after the progeny of initially damaged cells accumulate additional mutations.

• Ex/ natural UV radiation derived from the sun can cause skin cancers, because UV light can damage DNA by formation of pyrimidine dimmers. The DNA is usually repaired by a set of proteins that effect nucleotide excision repair. With extensive UV exposure the protein repair may be overwhelmed and skin cancers form.

Category: Pathology Notes