Capillary Fenestration in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced Rat Bladder Carcinoma is Promoted by Vascular Endothelial Growth Factor

Shin Wakui; Tomoko Muto; Hidetoshi Ohshige; Shinji Sasaki; Rie Ogasawara; Syunsuke Miyachi; Bungo Furusato; Hiroyuki Takahashi; Toshio Masaoka; Hiroshi Hano; Masakuni Furusato

doi:10.1293/tox.13.219

Originals

Capillary Fenestration in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced Rat Bladder Carcinoma is Promoted by Vascular Endothelial Growth Factor

Shin Wakui, Tomoko Muto, Hidetoshi Ohshige, Shinji Sasaki, Rie Ogasawara, Syunsuke Miyachi, Bungo Furusato, Hiroyuki Takahashi, Toshio Masaoka, Hiroshi Hano, Masakuni Furusato

Author information

Shin Wakui
Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato, Tokyo 105-8461 Japan
Tomoko Muto
Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
Hidetoshi Ohshige
Life Science Research Center, Lion Corporation, 100 Tajima, Odawara, Kanagawa 256-0811 Japan
Shinji Sasaki
Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
Rie Ogasawara
Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
Syunsuke Miyachi
Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
Bungo Furusato
Department of Pathology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku, Tokyo 160-0023 Japan
Hiroyuki Takahashi
Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato, Tokyo 105-8461 Japan
Toshio Masaoka
Comparative Toxicology Laboratories, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 229-8501 Japan
Hiroshi Hano
Department of Pathology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato, Tokyo 105-8461 Japan
Masakuni Furusato
Department of Pathology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 Japan

Keywords: fenestrated blood capillary, neutralizing antibody for vascular endothelial growth factor, N-butyl-N-(4-hydroxybutyl)nitrosamine, rat bladder carcinoma, microscopy electron

JOURNAL FREE ACCESS

2000 Volume 13 Issue 4 Pages 219-224

DOI https://doi.org/10.1293/tox.13.219

Details

Abstract

Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein that specifically increases vascular permeability and stimulates angiogenesis. Recently we demonstrated a high level of VEGF and VEGF mRNA expression in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder carcinomas with abundant fenestrated capillaries. We speculated that the expression of VEGF might be involved in the induction or maintenance of capillary fenestration, and examined ultrastructurally the morphological alteration of blood capillaries in BBN-induced rat bladder carcinoma following the administration of neutralizing antibody against VEGF. Five minutes after administration, the fenestrated endothelial cell ratio and the number of fenestrae decreased significantly, and continued to decrease with time reaching a minimum at 10 minutes after administration. The ratio thereafter gradually increased and at 30 minutes returned to its control condition. These results showed the specific inhibition of VEGF bioactivity potently induced to close the capillary fenestrations. We can suggest that VEGF synthesized by BBN-induced rat bladder carcinoma cells specifically induces and maintains the tumor capillary fenestrations.

Corresponding author