Spontaneous Mutagenesis: Experimental, Genetic and Other Factors

Spontaneous mutations are "the net result of all that can go wrong with DNA during the life cycle of an organism" (Glickman et al., 1986). Thus, the types and amounts of spontaneous mutations produced are the resultant of all the cellular processes that are mutagenic and those that are antimutagenic. It is not widely appreciated that the types and frequencies of spontaneous mutations change markedly with subtle changes in experimental conditions. All types of mutations are produced spontaneously, i.e., base substitutions, frameshifts, insertions and deletions. However, very few papers have appeared that are devoted exclusively to the study of the mechanisms of spontaneous mutagenesis, and of the subtle experimental factors that affect the types and frequencies of spontaneous mutations. This is unfortunate because spontaneous mutagenesis appears to play a major role in evolution, aging, and carcinogenesis. This review emphasizes subtle experimental variables that markedly affect the results of a spontaneous mutation experiment. A thorough understanding of these variables eliminates the need for a theory of "directed" mutagenesis. The intrinsic instability of DNA, and the types of normal metabolic lesions that are produced in DNA that lead to mutations via errors made in replication, repair, and recombination are reviewed, as is the genetic control of spontaneous mutagenesis. As with spontaneous mutagenesis, spontaneous carcinogenesis can also be considered to be the net result of all that can go wrong with DNA during the life of an organism.