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Two forms of repair in the DNA of human cells damaged by chemical carcinogens and mutagens.
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1974
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Ultraviolet RadiationDna DamageSummary Dna RepairRadiation EffectMolecular BiologyOxidative StressRadiation MedicineHuman CellsPhototoxicityToxicologyRadiation OncologyGenome InstabilityBiochemistryCancer GeneticsCell BiologyNatural SciencesChemical CarcinogensUv-c IrradiationMedicineMolecular MechanismsMutagenesis
DNA repair in human cells occurs in two distinct forms that depend on the type of DNA damage. The study aims to determine whether long‑repair involves an endonuclease acting on DNA distortions or intercalations. Short‑repair is characterized by simple excision and replacement of a few bases at a single‑strand break. Ionizing radiation and certain chemicals trigger rapid short‑repair inserting a few nucleotides, whereas ultraviolet radiation and other agents induce extensive long‑repair excising many bases over hours, and xeroderma pigmentosum cells show defective long‑repair.
Summary DNA repair in human cells, as assayed by the photolysis of 5-bromodeoxyuridine incorporated during repair, takes one of two limiting forms, depending on the nature of the original insult to the DNA. Damage from ionizing radiation is repaired by the insertion of three or four nucleotides during a brief period (∼60 min) after the insult, but in the case of ultraviolet radiation there is extensive excision of bases (∼100) during a protracted period (18 to 20 hr). Similarly, chemicals that damage DNA fall into two categories, those that result in the ionizing or “short” type of DNA repair (ethyl methanesulfonate, methyl methanesulfonate, propane sultone) and those that result in the ultraviolet or “long” type of repair (N-acetoxy-2-acetylaminofluorene, 2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino] acridine dihydrochloride). In addition, some chemicals (4-nitroquinoline 1-oxide) cause damage that apparently is repaired by both mechanisms. When agents that induce long repair in normal cells are used to treat cells from patients with the genetic disease xeroderma pigmentosum (characterized by extreme sensitivity to ultraviolet radiation), defective repair is seen. Thus it is possible that long repair involves the action of an endonuclease (thought to be lacking in xeroderma cells) on a distortion or intercalation in the DNA. Short repair may involve the simple excision and replacement of a few bases at the site of a single-strand break.