Very high frequency of lymphoma induction by a chemical carcinogen in pim-1 transgenic mice.
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.
Breuer
M
M
Division of Molecular Genetics, the Netherlands Cancer Institute, Amsterdam.
Slebos
R
R
Verbeek
S
S
van Lohuizen
M
M
Wientjens
E
E
Berns
A
A
D000818:Animals; D015152:Blotting, Northern; D005038:Ethylnitrosourea; D008223:Lymphoma / Q000139:chemically induced*; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes
D012333:RNA, Messenger; D005038:Ethylnitrosourea