The nature of spontaneous mutations.
The induction of mutations is often expressed in relation to spontaneous mutations and designated for instance by the doubling-dose concept. A problem in that context is the fact that the mutational spectrum for spontaneous and induced mutations is not the same and it can furthermore vary considerably between loci. This is illustrated by molecular characterization of spontaneous and ionizing-radiation-induced mutations in mammalian cells. Furthermore changes of the genetic machinery are not limited to those endpoints usually measured in mutational assays, that is, base substitutions, frameshifts, classical chromosomal aberrations and numerical alterations of chromosomes. Additional alterations, of which far less is known, include insertion mutations, recombinogenic events and disproportionate replication of DNA giving rise to gene amplifications, and changes of gene expression through methylation of cytosine. There are reasons to believe that these endpoints are of importance in the development of tumors. Amplification of oncogenes is a well-known phenomenon in tumorigenicity and lately mutations by the insertion of mobile DNA elements have been demonstrated in cancer cells. Often these alterations are induced by stress and they constitute a manifestation of the dynamics and instability of DNA and the genetic system revealed in recent years. It is of interest in that context that the flow of genetic information does not only occur in one direction that is, DNA-RNA-protein, but also from RNA to DNA through reverse transcription and possibly even from the protein end of the sequence.
Ramel
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Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, University of Stockholm, Sweden.
D000818:Animals; D006224:Cricetinae; D003412:Cricetulus / Q000235:genetics; D004247:DNA / Q000235:genetics; D004251:DNA Transposable Elements; D004330:Drosophila; D005784:Gene Amplification; D008322:Mammals / Q000235:genetics; D051379:Mice; D009154:Mutation; D012313:RNA / Q000235:genetics; D011995:Recombination, Genetic
D004251:DNA Transposable Elements; D012313:RNA; D004247:DNA