Enzymatic studies on binding of mutagenic principles in tryptophan pyrolysate to DNA.

DOI
  • SHISHIDO Kazuo
    Department of Microbiology, The Institute of Physical and Chemical Research
  • TACHIBANA Toshiaki
    Department of Microbiology, The Institute of Physical and Chemical Research
  • ANDO Tadahiko
    Department of Microbiology, The Institute of Physical and Chemical Research

抄録

It was evidenced that mutagenic principles in tryptophan pyrolysate, 3-amino-1, 4-dimethyl-5H pyrido(4, 3-b) indole and 3-amino-l-methyl-5H pyrido(4, 3-b) indole (abbreviated as Trp-P-1 and Trp-P-2, respectively) bind to DNA without activation by rat liver microsomes. The bindings of Trp-P-I and Trp-P-2 were not random and did not introduce strand scissions into DNA. Trp-P-1 bound more easily than Trp-P-2. The bindings of these mutagenic principles to DNA were concluded by using negatively superhelical simian virus 40 (SV40) DNA from following experimental data. (1) The intensity of ethidium bromide (EtBr)-DNA fluorescence by illumination with UV light and the electrophoretic mobility of superhelical DNA in agarose gel decreased as a function of the amounts of Trp-P-1 and Trp-P-2. (2) In vitro RNA synthesis catalyzed by Escherichia coli DNA-dependent RNA polymerase and nick-translation catalyzed by Escherichia coli DNA polymerase I (Kornberg enzyme) were inhibited significantly on DNA treated with Trp-P-I and Trp-P-2. (3) The negative superhelicity of SV40 DNA introduces unpaired regions into DNA. These regions can be cleaved by single-strand-specific Sl endonuclease to generate unit length linear duplex molecules. It was found that this Sl-sensitivity of DNA decreased by treatment with Trp-P-1. (4) The cleavage patterns of Trp-P-1 treated DNA with five restriction endonucleases were investigated. The protection of the cleavage site by the drug was observed against HincII, HindIII and EcoRII, whereas not against HaeIII and HinfI. These results show that the binding of Trp-P-1 to DNA is not random. Identical results were also obtained in Trp-P-2.<br> However, the bindings of Trp-P-1 and Trp-P-2 were not so tight, and phenol extraction of the complex dissociated these drugs from DNA.

収録刊行物

詳細情報 詳細情報について

  • CRID
    1390001206469617024
  • NII論文ID
    130003526912
  • DOI
    10.1271/bbb1961.44.1609
  • COI
    1:CAS:528:DyaL3cXlvVSmtLg%3D
  • ISSN
    18811280
    00021369
  • 本文言語コード
    en
  • データソース種別
    • JaLC
    • Crossref
    • CiNii Articles
  • 抄録ライセンスフラグ
    使用不可

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