Abstract

Alkylnitrosoureas, because of their chemical simplicity and known catabolism as well as their ability to induce a high incidence of neurogenic tumors with precision, provide an excellent opportunity to study the mechanism of induction and pathogenesis of neoplasms. This project utilizes marked variations in susceptibility and length of latency peroids observable between rat strains during transplacental induction of neurogenic tumors with ethylnitrosourea. Attempts will be made to correlate such variations in carcinogenic susceptibility with differing activities of gene processing by examining synthesis and induction of helix destabilizing protein and rec?-like protein in glial (target) and neuronal (non-target) cells of carcinogenically susceptible and resistant strains of rats. The precision of ethylnitrosourea in the neurogenic tumor induction will further be utilized in evaluating the role of nerve growth factor in regression of trigeminal neurinoma. It is also proposed to produce trigeminal neurinoma clones with nerve growth factor receptors, which will be used to further examine the morphological and biological effects of nerve growth factor upon anaplastic tumor cells of neural crest derivation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032594-04
Application #
3170494
Study Section
Pathology A Study Section (PTHA)
Project Start
1981-10-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Michigan State University
Department
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824

  Publications

Marushige, Y; Marushige, K; Koestner, A (1994) Growth inhibition of synchronized trigeminal neurinoma cells by nerve growth factor. Anticancer Res 14:153-6
Paul, D; Marushige, K (1994) Characterization of single-stranded DNA binding proteins in rat glial-enriched nuclei. Exp Mol Pathol 61:82-96
Marushige, Y; Marushige, K; Koestner, A (1992) Growth inhibition of anaplastic glioma cells by nerve growth factor. Anticancer Res 12:2069-73
Yaeger, M J; Koestner, A; Marushige, K et al. (1992) The use of nerve growth factor as a reverse transforming agent for the treatment of neurogenic tumors: in vivo results. Acta Neuropathol 83:624-9
Yaeger, M J; Koestner, A; Marushige, K et al. (1991) The reverse transforming effects of nerve growth factor on five human neurogenic tumor cell lines: in vitro results. Acta Neuropathol 83:72-80
Koestner, A (1990) Characterization of N-nitrosourea-induced tumors of the nervous system;their prospective value for studies of neurocarcinogenesis and brain tumor therapy. Toxicol Pathol 18:186-92
Raju, N R; Yaeger, M J; Okazaki, D L et al. (1990) Immunohistochemical characterization of rat central and peripheral nerve tumors induced by ethylnitrosourea. Toxicol Pathol 18:18-23
Marushige, Y; Marushige, K; Koestner, A (1989) Chemical control of growth and morphological characteristics of anaplastic glioma cells. Anticancer Res 9:1729-35
Marushige, Y; Marushige, K; Okazaki, D L et al. (1989) Cytoskeletal reorganization induced by nerve growth factor and glia maturation factor in anaplastic glioma cells. Anticancer Res 9:1143-8
Raju, N R; Koestner, A; Marushige, K et al. (1989) Effect of nerve growth factor on the transplacental induction of neurinomas by ethylnitrosourea in Sprague-Dawley rats. Cancer Res 49:7120-3

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