Key Concepts of Section 24.2

• Changes in the DNA sequence can result from DNA copying errors and the effects of carcinogens. All carcinogens are mutagens; that is, they act by altering one or more nucleotides in DNA.

• Indirect-acting carcinogens, the most common type of carcinogen, must be activated before they can damage DNA. In animals, metabolic activation occurs via the cytochrome P-450 system, a pathway generally used by cells to rid themselves of noxious foreign chemicals. Direct-acting carcinogens such as EMS and DMS require no such cellular modifications in order to damage DNA.

• Benzo(a)pyrene, a component of cigarette smoke, causes inactivating mutations in the p53 gene, thus contributing to the initiation of human lung tumors.

• The multi-hit model, which proposes that multiple mutations are needed to cause cancer, is consistent with the genetic homogeneity of cells from a given tumor, the observed increase in the incidence of human cancers with advancing age, and the cooperative effect of oncogenic transgenes and tumor-suppressor gene mutations on tumor formation in mice.

• Colon cancer develops through distinct morphological stages that are commonly associated with mutations in specific tumor-suppressor genes and proto-oncogenes.

• Cultured cells and mice in which oncogenes and tumor-suppressor genes can be expressed in a time- and tissue-specific manner teach us about how cancers arise and how these genes contribute to the development and progression of the disease.