Very high frequency of lymphoma induction by a chemical carcinogen in pim-1 transgenic mice

Nature. 1989 Jul 6;340(6228):61-3. doi: 10.1038/340061a0.

Abstract

Infection of mice with Moloney murine leukaemia virus (MuLV) induces T-cell lymphomas after an average latency period of 150 days. In these lymphomas the MuLV DNA is frequently integrated into the mouse chromosomal DNA in the vicinity of the pim-1 oncogene. Transgenic mice overexpressing the pim-1 oncogene are predisposed to develop T-cell lymphomas, but only to the extent that approximately 10% of the mice develop a lymphoma within 240 days. When these mice are infected with MuLV, lymphomas develop in all mice in only 50-60 days. In these lymphomas MuLV DNA is integrated near either the c-myc or N-myc gene, suggesting that pim-1 and myc synergize in lymphomagenesis. To determine whether this system has a more general application, we have now tested the susceptibility of pim-1 transgenic mice to N-ethyl-N-nitrosourea (ENU), a chemical carcinogen. With a single low dose of ENU, nearly all pim-1 transgenic mice, but only 15% of non-transgenic mice, develop T-cell lymphomas within 200 days. All ENU-induced lymphomas in both pim-1 transgenic and non-transgenic mice express high levels of c-myc messenger RNA, supporting the notion that pim-1 and c-myc synergize in lymphoma induction. We propose that pim-1 transgenic mice could be used to test the oncogenic potential of other chemical compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Ethylnitrosourea
  • Lymphoma / chemically induced*
  • Mice
  • Mice, Transgenic
  • Oncogenes*
  • RNA, Messenger / analysis
  • T-Lymphocytes*

Substances

  • RNA, Messenger
  • Ethylnitrosourea