Somatic cell mutations

Figure 6. The c-mos negative regulatory element (NRE). Nucleotide positions of the NRE are shown relative to the spermatocyte transcription start site, taken as 280 base pairs upstream of the c-mos ATG (see Fig. 4). The endpoints of the NRE are defined by deletions that allow c-mos expression in NIH 3T3 and other somatic cells. Mutations of the sequences designated by boxes 1,2, and 3 also allow c-mos transcription in NIH 3T3 cells, indicating that these sequences represent functional elements within the NRE. Boxes 1 and 2 are similar to sequences upstream of the protamine (Prot) promoter that inhibit in vitro transcription in HeLa cell extracts. A sequence just upstream of box 2 is also similar to a putative repressor-binding site in the regulatory region of Pgk2.

Unless otherwise stated, I use the terms "genetic" and "inherited" interchangeably to refer to the alleles that a person receives from his or her parents, and which could be transmitted to his or her children. I do not mean acquired somatic cell mutations or mutations in infectious agents. 

Strauss, G.H. and Albertini, R.J. (1979). Enumeration of 6-thioguanine-resistmt peripheral blood lymphocytes in man as a potential test for somatic cell mutations arising in vivo, "Mutat. Res. 61,353. 

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. 

Butadiene did not induce somatic cell mutation and recombination or sex-linked recessive lethal mutation in Drosophila melanogaster. 

In single in-vivo studies, catechol did not induce DNA strand breaks or somatic cell mutations in the mouse spot test (one study). On the other hand, micronuclei were induced in mouse bone marrow (three of four studies). In one of these positive micronucleus test studies, the effect was greater after intraperitoneal injection than after gavage administration, while, in the other positive study, the effect of an intraperitoneal injection was enhanced by either phenol or hydroquinone. 

The genotoxicity of sulfur mustard is well documented. It is known to produce DNA cross-hnks, mutations following replication or repair errors, chromosomal breaks, and chromosomal aberrations. Occupational exposures have been associated with increased frequencies of somatic cell mutations, sister chromatid exchanges, and chromosome abnormalities. Studies with rats indicate that subchronic inhalation or oral exposures can produce dominant lethal effects. 

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. 

In sexually reproducing animals like ourselves, mutations can be Inherited only If they are present In cells that potentially contribute to the formation of offspring. Such germ-line cells Include eggs, sperm, and their precursor cells. Body cells that do not contribute to offspring are called somatic cells. Mutations that occur In these cells never are Inherited, although they may contribute to the onset of cancer. Plants have a less distinct division between somatic and germ-line cells, since many plant cells can function In both capacities. 

Albertini, R. J. (1980). Drug-resistant l3nnphocytes in man as indicators of somatic cell mutation. Teratogenesis, Carcinogenesis, and Mutagenesis 1 25-48. 

Finally, possibilities for the study of somatic-cell mutation rates in man are emerging cf. Sutton, 1971, 1972). If these methods could be substituted for studies of germinal-cell mutation rates, this would be highly desirable, since they will involve only a fraction of the effort and expense. An absolute sine qua non of any use of somatic-cell mutation rates to monitor human populations is that there has been at le2ist one extensive study in which both somatic-cell and germinal-cell mutation rates have been studied simultaneously in the same population. 

---