Somatic cell-mutation theory

Furthermore, it is accepted that the somatic cell-mutation theory underlies chemical carcinogenesis. This theory presumes that there is an interaction between the carcinogen and DNA to cause a mutation (Fig. 6.49). This mutation is then fixed when the DNA divides. Further replication then provides a clone of cells with the mutation, which may become a tumor. 

Within the general concept of the somatic cell mutation theory, it is now clear that there are a number of different mechanisms underlying carcinogenesis. Thus, the carcinogen can interact with a number of processes, not only causing a mutation, but influencing DNA repair and cell proliferation, for example. Furthermore, it seems cancers arise from an accumulation of several mutations. 

The somatic cell mutation theory underlies chemical carcinogenesis so there is an interaction between the carcinogen and DNA to cause a mutation. 

Berenblum, I., and Shubik, P. (1949). An experimental study of the initiating state of carcinogenesis, and a re-examination of the somatic cell mutation theory of cancer. Br J Cancer 3(1), 109-118. 

The concept that cancer involves an alteration in the genetic material of a somatic cell (somatic mutation theory) was first introduced by Theodor Boveri in 1914. Boveri suggested that cancer was related to chromosome abnormalities in somatic cells. With respect to chemical carcinogenesis, James and Elizabeth Miller in the 1950 s and 1960s observed that a wide variety of structurally diverse chemicals could produce cancer in laboratory animals. They suggested that many of these diverse... 

The somatic mutation theory of carcinogenesis states that mutation of DNA within somatic cells is required for neoplasia. The major pieces of evidence supporting the somatic mutation theory of carcinogenesis are shown in Table 24.4. 

The somatic mutation theory is based, in part, on the idea that background radiation and/or various endogenous mutagens produce random chromosome damage in all cells. Over time, the genetic loci become sufficiently altered such that various critical functions fail and the cell dies. The fact that irradiation of laboratory animals results in accelerated aging and premature death lends some support to this hypothesis. However, since irradiation produces free radicals, it could be considered part of that theory. 

Deoxyribonucleic acid (DNA) has limited chemical stability. As a result, oxidative damage, hydrolysis, and nonenzymatic DNA methylation occur in vivo at significant rates (L6). Thus, another aspect of this theory is that of intrinsic somatic mutations and the ability of cells to repair the damage to both mitochondrial and nuclear DNA. Indeed, mammalian cells have an elaborate system of DNA repair enzymes which become less efficient with time. Thus, failure to repair damaged DNA or to "misrepair it could lead to gene inactivation or possible excision of... 

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