The Fhit tumor suppressor protein regulates the intracellular concentration of diadenosine triphosphate but not diadenosine tetraphosphate

To determine the role of the FHIT tumor suppressor gene product, a diadenos ine 5',5'''-P-1,P-3-triphosphate (Ap(3)A) hydrolase, in the regulation of t he concentration of Ap(3)A and diadenosine S',5'''-P-1,P-4-tetraphosphate ( Ap(4)A) in vivo, the levels of the adenosine(5')triphospho(5')nucleoside (A p(3)N) and adenosine(5')tetraphospho(5')nucleoside (Ap(4)N) families were m easured by luminometry in a number of human cell lines and correlated with the expression of Fhit determined by immunoblotting. Fhit-positive cells ha d no Ap(3)N or a very Low level of Ap(3)N, whereas most Fhit-negative cells had Ap(3)N in the range 0.2-0.9 pmol/10(6) cells. Ap(4)N (mean value, 0.17 pmol/10(6) cells) did not correlate with Fhit expression. The results sugg est that Fhit efficiently metabolizes Ap(3)A and Ap(3)N but not Ap(4)A or A p(4)N in vivo.