The tumor spectrum in FHIT-deficient mice

Mice carrying one inactivated Fhit allele (Fhit +/- mice) are highly suscep tible to tumor induction by N-nitrosomethylbenzylamine, with 100% of Fhit /- mice exhibiting tumors of the forestomach/ squamocolumnar junction vs. 2 5% of Fhit +/+ controls. In the current study a single N-nitrosomethylbenzy lamine dose was administered to Fhit +/+, +/-, and -/- mice to compare carc inogen 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% e xhibited tumors (average 3.3 tumors/mouse) of the forestomach and squamocol umnar 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 mic e have been observed for up to 2 years for spontaneous tumors. Fhit +/- mic e (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 observ ed in mice with one or both Fhit alleles inactivated suggests that Fhit may be a one-hit tumor suppressor gene in some tissues.