Detection of inducible nitric oxide synthase (iNOS) mRNA by RT-PCR in ATL patients and HTLV-I infected cell lines: clinical features and apoptosis byNOS inhibitor

Various tumors have been reported to express an inducible form of nitric ox ide synthase (iNOS), and nitric oxide (NO) may affect the clinicopathologic al features of these tumors. Previously, Burkitt's lymphoma and Epstein-Bar r virus (EBV)infected cells were shown to express iNOS constitutively at a low level. We analyzed iNOS expression by the reverse transcriptase-polymer ase reaction method (RT-PCR) in eight HTLVI-infected cell lines (five were AIL-derived lines and there were in vitro transformed lines), nine ATL pati ents (three were chronic, two were acute, and four were lymphoma type), and an HTLV-1-negative T cell line (CEM). In four ATL derived and in all three in vitro transformed cell lines, iNOS was expressed constitutively, but it was not expressed in CEM cells. Four out of nine ATL patients also showed iNOS expression. The expression of iNOS was found in all subtypes of ATL. T hree of four iNOS-positive patients had infiltration of ATL cells to organs such as skin, lung, or liver. In NOS inhibitor (NG-monomethyl-L-arginine: L-NMMA)-containing medium, an iNOS-positive ATL cell line (K3T) showed grow th inhibition and DNA ladder. Although only a limited number of patients wa s analyzed, our results suggest that NO may be involved in the invasive cha racter of ATL cells. The NOS inhibitor can induce apoptosis in an ATL cell line, as it does in EBV-infected cell lines.