Inhibitors of thymine nucleotide biosynthesis: antimetabolites that provoke genetic change via primary non-DNA targets

Mutat Res. 1996 Aug 17;355(1-2):129-40. doi: 10.1016/0027-5107(96)00026-7.


Folate antagonists and direct-acting inhibitors of thymidylate synthase are potent genotoxic antimetabolites. These agents induce genetic change not by attacking DNA, but by interfering with the control of DNA precursor metabolism. This review surveys the genetic effects attributable to selected representatives of this class of antimetabolites.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / toxicity*
  • Carcinogens / toxicity
  • Folic Acid Antagonists / toxicity*
  • Humans
  • Mutagens / toxicity*
  • Thymidylate Synthase / antagonists & inhibitors*
  • Thymine Nucleotides / biosynthesis


  • Antimetabolites, Antineoplastic
  • Carcinogens
  • Folic Acid Antagonists
  • Mutagens
  • Thymine Nucleotides
  • Thymidylate Synthase
  • thymidine 5'-triphosphate