ROLES OF NITRIC-OXIDE IN TUMOR-GROWTH

A subclone of the human colon adenocarcinoma cell line DLD-1, which gr ew reproducibly as subcutaneous tumors in nude mice, was isolated. Suc h cells, when engineered to generate nitric oxide (NO) continuously, g rew more slowly in vitro than the wild-type parental cells. This growt h retardation was reversed by the addition of N-iminoethyl-L-ornithine , In nude mice, however, the tumors from these cells grew faster than those derived from wild-type cells and were markedly more vascularized , suggesting that NO may act as part of a signaling cascade for neovas cularization. Recent observations that the generation of NO in human b reast and gynecological cancers correlates positively with tumor grade are consistent with this hypothesis, We suggest that NO may have a du al pro- and antitumor action, depending on the local concentration of the molecule.