title: X-rays mutate human lymphoblast cells at genetic loci that should respond only to point mutagens.
abstract: We have demonstrated that X-rays induce mutations at 4 of 5 genetic loci. 2 of these loci, which code for a mRNA synthesis factor (resistance to 5,6-dichlororibofuranosylbenzimidazole) and tubulin (resistance to podophyllotoxin), are "small-marker" loci, in that they theoretically respond only to mutations which eliminate a toxin-binding site while leaving the major function of the protein intact. Thus mutations induced by X-rays in these two loci are most likely due to base-pair substitution-type alterations. X-Rays did not induce mutations in the Na+/K+ ATPase (resistance to ouabain), another small-marker locus. Two other loci, hypoxanthine guanine phosphoribosyl transferase (resistance to 6-thioguanine) and thymidine kinase (resistance to trifluorothymidine), are "whole-gene" targets in that they theoretically respond to a wide variety of mutagenic changes. X-Rays induced dose-dependent increases in mutant fraction at both of these loci. Ethyl methanesulfonate (EMS), an agent thought to produce mutations primarily through a base-pair substitution mechanism, induced mutations at all genetic loci tested. The pattern of mutations at the small-marker loci induced by EMS was different than that induced by X-rays, suggesting that the specificities of the mutagens and/or of the loci are different.
mesh_terms: D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008214:Lymphocytes / Q000528:radiation effects*; D009154:Mutation / Q000528:radiation effects*; D011034:Podophyllotoxin / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014965:X-Rays
chemical_list: D004004:Dichlororibofuranosylbenzimidazole; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase; D000254:Sodium-Potassium-Exchanging ATPase; D011034:Podophyllotoxin