Induction of trifluorothymidine-resistant mutants by metal ions in L5178Y/TK+/- cells.
7 inorganic metal salts including magnesium chloride, cadmium chloride, nickel chloride, zinc chloride, cobalt(II) chloride, lead acetate, sodium arsenate, and the platinum coordination complex, trans-platinum(II) diaminedichloride, were tested for the potential to induce trifluorothymidine-resistant (TFTRes) mutants in L5178Y/TK+/- mouse lymphoma cell by directly exposing cells to varied doses of each compound for 3 h. Of these 8 chemicals, cadmium chloride, nickel chloride, and trans-platinum(II) diaminedichloride consistently produced dose-related increases in the absolute number of TFTRes mutants as well as increases in mutation frequencies at compound concentrations permitting greater than 20% survival. Trans-platinum(II) diaminedichloride was a particularly effective mutagen, comparable to the direct-acting mutagen, methyl methanesulfonate. 15 representative TFTRes mutant cell clones derived from cultures originally treated with either the cadmium, or nickel, or platinum compounds were first grown out for 7 days in nonselective medium, then verified as phenotypically stable TK-/- mutants by demonstrated cross-resistance to 5-bromodeoxyuridine and 100% sensitivity to the folate antagonist methotrexate in THMG medium. These results demonstrate that the soluble salts of 2 metals reported to be human carcinogens and 1 noble metal complex known to bind DNA are all mammalian cell mutagens as well.
D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007739:L Cells / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009532:Nickel / Q000494:pharmacology; D010984:Platinum / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D008670:Metals; D009153:Mutagens; D002104:Cadmium; D010984:Platinum; D009532:Nickel; D008274:Magnesium; D015032:Zinc; D001151:Arsenic