Bush__The_Essential_Physics_for_Medical_Imaging - Biomedical ...

the integration of regulatory signals. These signals govern processes within the cellcycle and regulate cellular proliferation. Most mutations result in abrogation of thenormal enzymatic activity of Ras, which causes a prolonged activation state andunregulated stimulation of Ras signaling pathways that either stimulate cell growthor inhibit apoptosis.Cancer is thought to occur as a multistep process in which the initiation of damagein a single cell leads to a preneoplastic stage followed by a sequence of events thatpermit the cell to successfully proliferate. All neoplasms and their metastases arecharacterized by unrestrained growth, irregular migration, and genetic diversity andare thought to be derivatives or clones of a single cell. It is assumed that there is nothreshold dose for the induction of cancer, because even a single ionization eventcould theoretically lead to molecular changes in the DNA that result in malignanttransformation and ultimately cancer. However, the probability of cancer developmentis far lower than would be expected from the number of initiating eventsbecause of host defense mechanisms and the possibility that all of the subsequentsteps required for expression of the malignant potential of the cell will not occur.Cancer formation can be thought of as occurring in three stages: (a) initiation,(b) promotion, and (c) progression. During initiation, a somatic mutational eventoccurs that is not repaired. This initial damage can be produced by radiation or anyof a variety of other environmental or chemical carcinogens. During the promotionstage, the preneoplastic cell is stimulated to divide. A promoter is an agent that byitself does not cause cancer but, once an initiating carcinogenic event has occurred,promotes or stimulates the cell containing the original damage.There are more than 60 chemical or physical agents known to be carcinogenicin humans, including benzene, formaldehyde, vinyl chloride, and asbestos. Another200 or more agents are classified as "reasonably anticipated to be human carcingens."Unlike most carcinogens, radiation may act as an initiator or a promoter.Some hormones act as promoters by stimulating the growth of target tissues. Forexample, estrogen and thyroid-stimulating hormone may act as promoters of breastcancer and thyroid cancer, respectively.The final stage is progression, during which the transformed cell produces anumber of phenotypic clones, not all of which are neoplastic. Eventually, one phenotypeacquires the selective advantage of evading the host's defense mechanisms,thus allowing the development of a tumor and possibly a metastatic cancer. Radiationmay also enhance progression by immunosuppression.Environmental factors implicated in the promotion of cancer includetobacco, alcohol, diet, sexual behavior, air pollution, and bacterial and viral infections.Support for the role of environmental factors comes from observations suchas the increased incidence of colon cancer among Japanese immigrants to theUnited States compared with those living in Japan. Any agents that compromisethe immune system, such as the human immunodeficiency virus (HIV), increasethe probability of successful progression of a preneoplastic cell into cancer. Anumber of chemical agents, when given alone, are neither initiators nor promotersbut when given in the presence of an initiator will enhance cancer development.Many of these agents are present in cigarette smoke, which may in partaccount for its potent carcinogenicity. Environmental exposure to nonionizing