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{micro}-pim-1 transgenic mice

The usefulness of transgenic Eµ-pim-1 mice over-expressingthe pim-1 oncogene in lymphoid tissues, as sensitive test organismswas studied in a short-term carcinogenicity study. The micewere fed standard diet Altromin 1314 supplemented either with0.03% 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 formedduring cooking of meat and fish and are mutagenic to bacteriaand cultured mammalian cells. PhIP is a potent mouse lymphomagen,while IQ is a liver carcinogen and also causes lung tumors andtumors of the forestomach in mice. We found that transgenicEµ-pim-1 mice are highly susceptible to PhIP induced lymphomagenesisbut do not respond to the IQ treatment. PhIP feeding of Eµ-pim-1mice not only increased the total number of T-cell lymphomasbut also decreased the latency time compared to either transgenicor wild-type controls. The effect was most pronounced in thetreated female Eµ-pim-1 mice, which showed a higher incidenceof PhIP induced T-cell lymphomas than transgenic males and astrongly reduced latency period after PhIP treatment comparedto non-transgenic mice. Our results suggest that the transgenicEµ-pim-1 mouse may be a useful model for short-term carcinogenicityscreening of potential genotoxic carcinogens having the lymphoidsystem as target tissue. The carcinogen IQ which does not havethe lymphoid system as a target was not recognized in this model.