Arsenic trioxide causes selective necrosis in solid murine tumors by vascular shutdown.
To investigate the antitumor action of arsenic trioxide in solid tumors, we carried out quantitative tumor perfusion studies, using locally advanced methylcholanthrene-induced fibrosarcoma grown in BALB/c mice. The tumor perfusion studies were assessed by two separate methods: 99mTc clearance and 86Rb uptake. A single administration of arsenic trioxide (10 mg/kg i.p.) produced a preferential vascular shutdown in the tumor tissue at 2 and 6 h, leading to massive necrosis in the central part of the tumor. The phenomenon was repeatable at intervals of weekly administration of the drug in the same tumor. Normal skin, muscle, and kidney were relatively unaffected by arsenic trioxide. These results suggest that the drug may be investigated as an adjunct to the standard cancer therapeutic modalities.
Lew
Y S
YS
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA. younglew@yahoo.com
Brown
S L
SL
Griffin
R J
RJ
Song
C W
CW
Kim
J H
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects / Q000627:therapeutic use*; D001692:Biological Transport; D004195:Disease Models, Animal; D005354:Fibrosarcoma / Q000098:blood supply / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D010087:Oxides / Q000009:adverse effects / Q000627:therapeutic use*; D010477:Perfusion
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D008748:Methylcholanthrene; D000077237:Arsenic Trioxide