A possible role for deoxyribonucleotide pool imbalances in carcinogenesis.
Thymine nucleotide pool alterations, produced by attack on non-DNA primary targets, induce a variety of chromosome and chromatid aberrations. Specifically, in lower eukaryotes, thymidylate deprivation and excess are recombinagenic and dTMP depletion also produces DNA strand breakage. In higher eukaryotes, imbalances in thymine nucleotide pools provoke chromosome breaks and rearrangements, and inhibition of thymidylate biosynthesis causes morphological and oncogenic transformation in vitro. Thus, chromosomal rearrangements induced by dTMP deprivation may be the critical changes that lead to oncogenic transformation in response to thymine nucleotide depletion.
D000818:Animals; D002869:Chromosome Aberrations; D006801:Humans; D009369:Neoplasms / Q000209:etiology*; D013942:Thymine Nucleotides / Q000378:metabolism*
D013942:Thymine Nucleotides