The tumor spectrum in FHIT-deficient mice.
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.
Zanesi
N
N
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
Fidanza
V
V
Fong
L Y
LY
Mancini
R
R
Druck
T
T
Valtieri
M
M
Rüdiger
T
T
McCue
P A
PA
Croce
C M
CM
Huebner
K
K
D017766:Acid Anhydride Hydrolases; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000633:toxicity; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D002273:Carcinogens; D004128:Dimethylnitrosamine; D009363:Neoplasm Proteins; D011506:Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C014707:nitrosobenzylmethylamine