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UPTAKE OF BLEOMYCIN BY ETHYLNITROSOUREA-INDUCED RAT BRAIN TUMORS Kenkichi Horibata 1 , Yukitaka Ushio 1 , Toru Hayakawa 2 , Kazuyoshi Morimoto 1 , Norio Arita 1 , Toshio Yoshimine 2 , Heitaro Mogami 1 1Department of Neurosurgery, Osaka University Medical School 2Department of Neurosurgery, The Center for Adult Diseases pp.779-785
Published Date 1979/8/1
DOI https://doi.org/10.11477/mf.1406204451
  • Abstract
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The uptake of systemically administered bleo-mycin by 1-ethyl-l-nitrosourea-induced tumors of the central nervous system in rats were assayed by the paper disc method using B. subtilis PCI 219 IMC spores as the test organism.

Brain tumors were induced by subcutaneous in-jection of 1-ethyl-l-nitrosourea in S. D. rats within 3 days after birth at a dose of 50 mg per kg of body weight.

Forty-three symptomatic animals were admini-stered with bleomycin at a dose of 0.1 g per kg of body weight via the tail vein, and sacrificed by exsanguination two hours later. All animals were autopsied, and the induced tumors and normal tissues were removed from various organs for bio-assay of bleomycin. The adjacent tissues were fix edin either 10% formalin or 95% alcohol, and histo-logic sections were stained with hematoxylin and eosin, phos photungstic acid hematoxylin, Laidlow's method for connective tissue and immunofiuoresc-ence or immunoperoxidase using antiserum toAstroprotein.

Active form of bleomycin was detected in all induced tumors which consisted of 11 gliomas of the brain. 11 gliomas of the spinal cord, 14 schwannomas of the trigeminal nerve and 4 pitui-tary adenomas ; they were induced 8.0±0.5 (mean ±SEM), 8.1±0.6, 7.3±1.0 and 14.9±1.3 months after the subcutaneous administration of 1-ethyl-1-nitrosourea, respectively.

The average levels of bleomycin in the tumors were 7.69±2.84 mcg/g in gliomas of the brain, 7.10±3.15 mcg/g in gliomas of the spinal cord, 5.40 ±1.41 mcg/g in schwannomas of the trigeminal nerve and 4.83±1.05mcg/g in pituitary adenomas.

The tumor-plasma concentration ratio of bleo-mycin was 0.13±0.05 in gliomas of the brain, 0.27 ±0.12 in gliomas of the spinal cord, 0.23±0.05 inschwannomas of the trigeminal nerve and 0.21±0.08 in pituitary adenomas. The uptake of bleo-mycin by the normal brain and spinal cord was nill or trace. The average levels of bleomycin in normal tissues of various organs were: trigeminal nerve, 2.01±0.47 mcg/g; pituitary gland, 0.20±0.16 mcg/g; liver, 0.61±0.46 mcg/g; lung, 7.20±1.07 mcg/g ; spleen, 0.64±0.56 mcg/g; skin, 11.30±1.79 mcg/g and kidney, 37.01±6.46 mcg/g.

These findings are similar to those seen in our previous studies concerning the uptake of bleo-mycin by human brain tumors, and suggests that the 1-ethyl-1-nitrosourea-induced brain tumor in rats is an useful experimental model for the study of drug distribution in brain tumors.


Copyright © 1979, Igaku-Shoin Ltd. All rights reserved.

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電子版ISSN 2185-405X 印刷版ISSN 0006-8969 医学書院

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