Mutagenic mechanisms in leukemia and cancer: a new concept Cytosine lack could be as mutagenic as cytosine deamination

Abstract

The molecular mechanisms involved in mutagenesis caused by nitrous acid, ultraviolet light and cytosine methylation are reviewed. All three mutagens lead to a G=C --> A=T point mutation in the DNA molecule and the biochemical basis of these mutations in each case is the deamination of cytosine to uracil. It is shown that the lack of cytosine could be as mutagenic as the deamination of cytosine and it is shown schematically how cytosine lack could give rise to a population of genetically abnormal cells which are completely incapable of any degree of differentiation; a state perhaps reminiscent of the most acute of leukemias and the most anaplastic of cancers. A metabolic block in the amination of uracil to cytosine is suggested as a possible cause of the cytosine lack, a block which is unique in that it incorporates a mutagenic mechanism.