Abstract

A genotoxic event is a stable alteration in gene structure or function in surviving cells. This stable alteration is usually caused by a genetic change, that is, an alteration in the nucleotide sequence of the genomic DNA, but stable epigenetic changes are also conceivable. Stable epigenetic changes are caused by the alterations in the pattern of DNA methylation or by alteration in feedback control loops. An alteration in a DNA nucleotide sequence occur spontaneously as an error in DNA replication or recombination or is induced by agents that stimulate errors in DNA replication or recombination. Thus, the genotoxic potency of an agent is directly proportional to its mutagenic and recombinogenic capacity but inversely proportional to its toxic (cell-killing) effect; this is because genotoxic effects are obviously carried by altered surviving cells and not by dead cells. The chapter reviews the cellular molecular mechanisms that affect the frequency and the nature of genotoxic events.

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