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

Area of Science:

• Oncology
• Virology
• Genetics

Background:

• Moloney murine leukaemia virus (MuLV) infection causes T-cell lymphomas in mice with a long latency period.
• The pim-1 oncogene is often found near MuLV DNA integrations in these lymphomas.
• Transgenic mice overexpressing pim-1 are predisposed to T-cell lymphomas, but viral infection significantly shortens latency.

Purpose of the Study:

• To investigate the synergistic role of pim-1 and myc oncogenes in lymphomagenesis.
• To evaluate the utility of pim-1 transgenic mice for assessing chemical carcinogen oncogenic potential.

Main Methods:

• Infection of pim-1 transgenic and non-transgenic mice with MuLV.
• Administration of a single low dose of the chemical carcinogen N-ethyl-N-nitrosourea (ENU) to pim-1 transgenic and non-transgenic mice.
• Analysis of lymphoma development, latency periods, and oncogene expression (pim-1, c-myc, N-myc) in induced tumors.

Main Results:

• MuLV infection in pim-1 transgenic mice led to rapid T-cell lymphoma development in all mice, with MuLV DNA integrating near c-myc or N-myc.
• ENU exposure induced T-cell lymphomas in nearly all pim-1 transgenic mice, compared to only 15% of non-transgenic controls, within 200 days.
• All induced lymphomas, regardless of genotype or induction method, showed high c-myc messenger RNA levels, supporting pim-1 and c-myc synergy.

Conclusions:

• The pim-1 oncogene synergizes with c-myc in the induction of T-cell lymphomas.
• Pim-1 transgenic mice serve as a sensitive model for evaluating the oncogenic potential of chemical compounds.
• This model system advances our understanding of lymphomagenesis and offers a platform for carcinogenicity testing.