Use of E mu-PIM-1 transgenic mice short-term in vivo carcinogenicity testing: lymphoma induction by benzo[a]pyrene, but not by TPA

Carcinogenesis
E D KroeseC F van Kreijl

Abstract

E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to their low spontaneous tumour incidence and their increased sensitivity towards the lymphomagen ethylnitrosourea these mice may present an interesting model for short-term carcinogenicity testing. Here, we report on the further exploration of this transgenic mouse model with two additional carcinogens known to have, among others, the lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and 12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week (by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1 mice during the observation period of 40 weeks. B[a]P also induced tumours of the forestomach within this observation period, though at a lower incidence and apparently equally effective in wildtype and transgenic mice. TPA, on the other hand, was unable to induce lymphomas (or tumours in any other organ) in either transgenic or wildtype animals within the observation period of 44 weeks, when applied dermally at the maximum tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular analysis showed that B[a]P-induced lymphomas in...Continue Reading

Citations

Mar 18, 2000·Toxicology Letters·J Alexander
Jul 19, 2006·Pharmacogenetics and Genomics·Lindsay M MortonSophia S Wang
Mar 4, 2000·Environmental Health Perspectives·J McCannC N Rafferty
Feb 24, 1999·Molecular Carcinogenesis·C W van der Houven van OordtM L Breuer
Dec 24, 1998·Toxicologic Pathology·C F van KreijlR D Storer
Sep 2, 2006·Alternatives to Laboratory Animals : ATLA·Nirmala Bhogal, Robert Combes

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