Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in E(mu)-pim-1 transgenic mice

Carcinogenesis. 1996 Oct;17(10):2221-7. doi: 10.1093/carcin/17.10.2221.

Abstract

The usefulness of transgenic E(mu)-pim-1 mice over-expressing the pim-1 oncogene in lymphoid tissues, as sensitive test organisms was studied in a short-term carcinogenicity study. The mice were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months. PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver carcinogen and also causes lung tumors and tumors of the forestomach in mice. We found that transgenic E(mu)-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to the IQ treatment. PhIP feeding of E(mu)-pim-1 mice not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E(mu)-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males and a strongly reduced latency period after PhIP treatment compared to non-transgenic mice. Our results suggest that the transgenic E(mu)-pim-1 mouse may be a useful model for short-term carcinogenicity screening of potential genotoxic carcinogens having the lymphoid system as target tissue. The carcinogen IQ which does not have the lymphoid system as a target was not recognized in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenicity Tests / methods*
  • Carcinogens / toxicity*
  • Dose-Response Relationship, Drug
  • Enhancer Elements, Genetic
  • Female
  • Imidazoles / toxicity*
  • Lymphocytes / physiology
  • Lymphoma / chemically induced*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-pim-1
  • Quinolines / toxicity*
  • Sex Factors
  • Time Factors

Substances

  • Carcinogens
  • Imidazoles
  • Proto-Oncogene Proteins
  • Quinolines
  • 2-amino-3-methylimidazo(4,5-f)quinoline
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • Pim1 protein, mouse
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1