Related Experiment Video
Updated: Aug 4, 2026
Using Micro-computed Tomography for the Assessment of Tumor Development and Follow-up of Response to Treatment in a Mouse Model of Lung Cancer
Published on: May 20, 2016
The tumor spectrum in FHIT-deficient mice
Abstract:
Mice carrying one inactivated Fhit allele (Fhit +/- mice) are highly susceptible to tumor induction by N-nitrosomethylbenzylamine, with 100% of Fhit +/- mice exhibiting tumors of the forestomach/squamocolumnar junction vs. 25% of Fhit +/+ controls. In the current study a single N-nitrosomethylbenzylamine dose was administered to Fhit +/+, +/-, and -/- mice to compare carcinogen susceptibility in +/- and -/- Fhit-deficient mice. At 29 weeks after treatment, 7.7% of wild-type mice had tumors. Of the Fhit -/- mice 89.5% exhibited tumors (average 3.3 tumors/mouse) of the forestomach and squamocolumnar junction; half of the -/- mice had medium (2 mm diameter) to large (>2 mm) tumors. Of the Fhit +/- mice 78% exhibited tumors (average 2.4 tumors/mouse) and 22% showed medium to large tumors. Untreated Fhit-deficient mice have been observed for up to 2 years for spontaneous tumors. Fhit +/- mice (average age 21 mo) exhibit an average of 0.94 tumors of different types; Fhit -/- mice (average age 16 mo) also showed an array of tumors (average 0.76 tumor/mouse). The similar spontaneous and induced tumor spectra observed in mice with one or both Fhit alleles inactivated suggests that Fhit may be a one-hit tumor suppressor gene in some tissues.
Insights
Mice lacking functional Fhit (the tumor suppressor gene) showed increased susceptibility to carcinogen-induced tumors. These findings suggest Fhit may act as a one-hit tumor suppressor in certain tissues.
Area of Science:
- Oncology
- Genetics
- Carcinogenesis
Background:
- The Fragile Histidine Triad (Fhit) gene is a known tumor suppressor.
- Fhit deficiency in mice increases susceptibility to carcinogen-induced tumors.
Purpose of the Study:
- To compare carcinogen susceptibility in Fhit-deficient mice with one (Fhit +/-) or both (Fhit -/-) inactivated alleles.
- To investigate the role of Fhit as a one-hit tumor suppressor gene.
Main Methods:
- Mice with wild-type (Fhit +/+), heterozygous (Fhit +/-), and homozygous (Fhit -/-) Fhit genotypes were administered N-nitrosomethylbenzylamine.
- Tumor incidence and characteristics were assessed 29 weeks post-treatment.
- Spontaneous tumor development was monitored in untreated Fhit-deficient mice for up to 2 years.
Main Results:
- Fhit -/- mice exhibited an 89.5% tumor incidence with an average of 3.3 tumors per mouse, primarily in the forestomach and squamocolumnar junction.
- Fhit +/- mice showed a 78% tumor incidence with an average of 2.4 tumors per mouse.
- Wild-type mice had a significantly lower tumor incidence (7.7%).
- Both Fhit +/- and Fhit -/- mice developed spontaneous tumors, indicating Fhit's role in tumor suppression.
Conclusions:
- Fhit deficiency significantly enhances susceptibility to carcinogen-induced tumors.
- The similar tumor spectra in Fhit +/- and Fhit -/- mice suggest Fhit may function as a one-hit tumor suppressor in certain tissues.
- These findings underscore the importance of Fhit in preventing tumor development.
