Effects of NG-nitro-L-arginine and/or L-arginine on experimental pulmonary metastasis in mice.
Effects of NG-nitro-L-arginine methyl ester (L-NAME; an inhibitor of nitric oxide (NO) synthase) and/or L-arginine (substrate of NO synthase) on pulmonary metastasis of murine melanoma and Lewis lung carcinoma cells were investigated. L-NAME, L-arginine or both L-NAME and L-arginine was injected i.p. into mice 5, 3, and 1 h before and 1, 3, 5, and 7 h after the injection of tumor cells into mice via a tail vein. The administration of L-NAME (9.3 mumol/mouse) alone or L-arginine alone (46.5 or 186 mumol/mouse) potentiated pulmonary metastasis of highly and poorly metastatic B16 melanoma cells. L-NAME alone also increased the number of pulmonary metastasis of Lewis lung carcinoma cells, but L-arginine (185 mumol/mouse) did not. However, the combination of L-NAME and L-arginine increased the number of pulmonary metastasis of both the melanoma and Lewis lung carcinoma cells synergistically. L-NAME or L-arginine administration enhanced the retention of B16 melanoma cells in the lungs examined 24 h after the tumor cell injection. Synergistic effect of L-NAME and L-arginine was also seen in the tumor cell retention. The present results suggest that the metastatic potentials of the tumor cells do not simply correlate to NO production in vivo.
Yamamoto
T
T
Department of Pathology, Center for Adult Diseases, Osaka, Japan.
Terada
N
N
Nishizawa
Y
Y
Tanaka
H
H
Akedo
H
H
Seiyama
A
A
Shiga
T
T
Kosaka
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000633:toxicity*; D004357:Drug Synergism; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D018328:Melanoma, Amelanotic / Q000517:prevention & control / Q000556:secondary*; D008546:Melanoma, Experimental / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000473:pathology; D013047:Specific Pathogen-Free Organisms
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester