Induction of DNA recombination by activated 3-amino-1-methyl-5H-pyrido[4,3-b]indole

Jpn J Cancer Res. 1995 Feb;86(2):155-9. doi: 10.1111/j.1349-7006.1995.tb03033.x.

Abstract

To investigate the genotoxic properties of a food-derived carcinogen, 3-amino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2), we have tested whether Trp-P-2 and its metabolically transformed products can induce DNA recombinations. Trp-P-2 is a strong mutagen and its activated form, the N-hydroxylated derivative, Trp-P-2(NHOH), is known to form DNA adducts and cause DNA chain cleavage. Using a system in which phage lambda undergoes recombination inside host Escherichia coli, we have found that Trp-P-2(NHOH), but not Trp-P-2 itself, can induce recombination. A nitroso derivative of Trp-P-2, Trp-P-2(NO), which can be reduced intracellularly to form Trp-P-2(NHOH), also induced recombination. Active oxygens are implicated in this recombinogenic action, since Trp-P-2(NHOH) is known to undergo spontaneous oxidative degradation, generating active oxygen radicals which can cause DNA chain cleavages. 4-Hydroxyaminoquinoline N-oxide and phenyl-hydroxylamine also showed recombinogenic actions in this assay system; hence, it is suspected that aromatic amine-type carcinogens have this property in common.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophage lambda / drug effects*
  • Bacteriophage lambda / radiation effects
  • Carbolines / pharmacology*
  • Carcinogens / pharmacology*
  • DNA Damage*
  • DNA, Viral / drug effects*
  • DNA, Viral / radiation effects
  • Escherichia coli / virology
  • Mutagens / pharmacology*
  • Recombination, Genetic*

Substances

  • Carbolines
  • Carcinogens
  • DNA, Viral
  • Mutagens
  • 3-amino-1-methyl-5H-pyrido(4,3-b)indole