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Mutagenic activation reduces carcinogenic activity of ortho-aminoazotoluene for mouse liver

L P Ovchinnikova1, L A Bogdanova, V I Kaledin

  • 1Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia.

Bulletin of Experimental Biology and Medicine
|May 10, 2013
PubMed

Insights

Pentachlorophenol inhibited the liver cancer activity of aromatic amines like 4-aminoazobenzene and ortho-aminoazotoluene in mice. This suggests the parent compound, not its metabolites, is the primary liver carcinogen.

Area of Science:

  • Toxicology
  • Hepatocarcinogenesis
  • Metabolic enzyme induction

Background:

  • Aromatic amines are known carcinogens, with their activity often modulated by metabolic processes.
  • Pentachlorophenol is recognized as an inhibitor of metabolic enzyme stimulation.

Purpose of the Study:

  • To investigate the effect of pentachlorophenol on the hepatocarcinogenic activity of 4-aminoazobenzene and ortho-aminoazotoluene.
  • To elucidate the role of metabolic activation in the carcinogenicity of ortho-aminoazotoluene.

Main Methods:

  • Administration of 4-aminoazobenzene and ortho-aminoazotoluene to suckling mice.
  • In vitro mutagenicity testing using Ames' test (S. typhimurium TA 98 strain) with liver enzyme activation.
  • Assessment of pentachlorophenol's effect on carcinogenicity and mutagenicity.

Main Results:

  • Pentachlorophenol significantly reduced the liver tumor-inducing potential of both 4-aminoazobenzene and ortho-aminoazotoluene.
  • Pentachlorophenol suppressed the mutagenic activity of these compounds in the Ames' test.
  • Enzyme induction that enhanced ortho-aminoazotoluene's mutagenicity concurrently reduced its carcinogenic effect.

Conclusions:

  • The parent compound, ortho-aminotoluene, is identified as the direct hepatocarcinogen in mice, rather than its mutagenic metabolites.
  • Pentachlorophenol acts as an inhibitor, reducing the carcinogenic and mutagenic potential of these aromatic amines.

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