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Nitrofuran induced mutagenesis and error prone repair in Escherichia coli
Authors:DW Bryant  DR McCalla
Affiliation:Department of Biochemistry, McMaster University, Hamilton, Ontario, L8S 4J9 Canada
Abstract:The binding of cis(c)- and trans(t)-Pt(NH3)2Cl2 to DNA at platinum/DNA-nucleotide ratios (Ri) of 0.1 or less has been studied by means of radioactive 195mPt-labeled compounds. Kinetic data are consistent with the following scheme:
/></figure> At 25°C and pH 5–6 in 5 mM NaClO<sub>4</sub>, the values for the rate constants in the above scheme for the <em>c</em>-isomer are <em>k</em><sub>2</sub> = 2.2 × 10<sup>?5</sup> sec<sup>?1</sup>, <em>k</em><sub>7</sub> = 0.32 (sec M)<sup>?1</sup>, and <em>k</em><sub>8</sub> = 143 (sec M)<sup>?1</sup>; for the <em>t</em>-isomer the values are <em>k</em><sub>2</sub> < 0.5 × 10<sup>?5</sup> sec<sup>?1</sup> and <em>k</em><sub>7</sub> = 0.95 (sec M)<sup>?1</sup>. Platinum-DNA adducts do not undergo detectable exchange after 3 days at 37°C, indicating the absence of a dynamic equillibrium. For both isomers the rate of binding is the same for single- and double-stranded DNA. The conclusions derived from Ag<sup>+</sup> and H<sup>+</sup> titration studies are consistent with binding at guanine N(7) for <em>R</em><sub>i</sub> < 0.1. The reaction rate is competitively inhibited by various salts and buffers and is suppressed by raising the pH (50% inhibition of initial rates at pH 7.3). At 37°C and pH 7 in 0.15 M NaCl, 6–8% of both the <em>c</em>- and <em>t</em>-isomers bind to DNA in 24 h, suggesting that both compounds should bind to DNA under biological conditions.</td> </tr> <tr> <td align=
Keywords:c  cis  t  trans  Am  Aq  molecules of bound platinum/DNA-nucleotide  total number of atoms of platinum/DNA-nucleotide
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