Spontaneous mutations, origination

The choice of the strain of microorganism is one of the important variables in the process. The strains to be used in manufacture are mutants of the original producer, which are chosen as the result of a planned program of mutant selection. Sometimes a spontaneous mutation occurs usually, it is induced by mutagenic agents or irradiation of various sorts. The choice of the best strain depends on its abiUty to produce large amounts of the proper antibiotic in a reasonable time from ingredients that are economically feasible (73). 

Inoculate serial log10 dilutions of the original stock in the sixth well, for detection of spontaneous mutations owing to passaging. 

Crow JF. The origins, patterns and impHcations of human spontaneous mutation. Nat Rev Genet 2000 1 40-7. 

Current data support a clonal origin of most cancers because most tumors arise from a single cell as a result of a spontaneous mutation or after exposure to an oncogenic virus or chemical carcinogen these tumors then expand to a detectable level while continually shedding viable cells. The ability to cure the cancer then depends on numerous variables, the most important being the presence of viable metastasis. The application of chemotherapy arose out of the appreciation that cancer is not commonly a localized process and is thus not amenable to control... 

Eukaryotic DNA Transposons McCllntock s original discovery of mobile elements came from observation of certain spontaneous mutations in maize that affect production of any of the several enzymes required to make anthocyanln, a purple pigment in maize kernels. Mutant kernels are white, and wild-type kernels are purple. One class of these mutations is revertlble at high frequency, whereas a second class of mutations does not revert unless they occur in the presence of the first class of mutations. McClintock called the agent responsible for the first class of mutations the activator (Ac) element and those responsible for the second class dissociation (Ds) elements because they also tended to be associated with chromosome breaks. 

Overall, these data raise the possibility that most of the mutations in breast cancer might have a spontaneous origin, but that a small proportion of them bear signatures that suggest the involvement of exogenous carcinogens such as those present in tobacco smoke. These proposals await scrutiny by the analysis of large cohorts with defined exposure histories. 

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