Effect of cis-platinum(II)diamminodichloride on wild type and deoxyribonucleic acid repair deficient mutants of Escherichia coli.
The anti-tumor drug cis-platinum(II)diamminodichloride (PDD) induced extensive filamentation in wild-type Escherichia coli and in mutants lacking certain deoxyribonucleic acid (DNA) repair functions (uvrA, recB, recC, and polA); viability of repair-deficient mutants treated with PDD was significantly less than that of wild-type cells. PDD was highly toxic to lex1, lex1 uvrA6 (where its effect was cummulative), and recA13 mutants, all of which were killed without formation of filaments. (3)H-thymine incorporated into DNA of cells subsequently treated with PDD became trichloroacetic acid-soluble at rates similar to those observed after exposure to comparable doses of ultraviolet light (UV) or mitomycin C. PDD, like UV, induced extensive degradation of DNA in recA organisms. After a 30-min lag, PDD inhibited significantly the synthesis of DNA but not of ribonucleic acid or protein in E. coli. However, the relative differences between rates of DNA synthesis observed in PDD-treated and control cells decreased substantially when the duration of pulses ((3)H-thymine) was prolonged from 2 to 5 min. These observations suggest that PDD-induced damage to DNA is reversible, possibly by defined mechanisms of excision and recombination repair.
D001426:Bacterial Proteins / Q000096:biosynthesis; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D004260:DNA Repair; D004269:DNA, Bacterial / Q000096:biosynthesis*; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D007532:Isoleucine / Q000378:metabolism; D008937:Mitomycins / Q000494:pharmacology; D009154:Mutation; D009691:Nucleic Acid Denaturation; D012329:RNA, Bacterial / Q000096:biosynthesis; D011830:Radiation Effects; D013053:Spectrophotometry; D013696:Temperature; D013941:Thymine / Q000378:metabolism; D014316:Tritium; D014466:Ultraviolet Rays; D014498:Uracil / Q000378:metabolism
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008937:Mitomycins; D012329:RNA, Bacterial; D007532:Isoleucine; D014316:Tritium; D014498:Uracil; D002945:Cisplatin; D013941:Thymine