Sprague-Dawley (CD) rats were injected intravenously with ethylnitrosourea at a dose of 20 mg/kg on day 20 of gestation. This exposure resulted in early neoplastic proliferation or development of a neurinoma of the trigeminal nerve in 58% of the offspring at 90 days of age. Implantation of osmotic microinfusion pumps containing 2.5S nerve growth factor prior to ethylnitrosourea administration significantly reduced the incidence of early neoplastic proliferation. Postnatal implantation of microinfusion pumps containing 2.5S nerve growth factor also resulted in a significant but less pronounced reduction of early neoplastic proliferation. Immunoglobulin G directed against nerve growth factor (anti-nerve growth factor) did not influence the incidence of early neoplastic proliferation when administered via microinfusion pumps implanted on day 15 postnatally. These findings suggest that nerve growth factor has a protective effect on the developing nervous system against ethylnitrosourea-induced carcinogenesis.
References
1.
BocchiniV.AngelettiP. U.:
The nerve growth factor: Purification of a 30, 000 molecular weight protein.Proc Natl Acad Sci (USA)61:
787–794,
1969
2.
BoonstraJ.Van Der SaagP.MoolenaarW.DelaatS.:
Rapid effects of nerve growth factor on the Na+, K+- pump in rat pheochromocytoma cells.Exp Cell Res131:
452–455,
1981
3.
BuekerE. D.:
Implantation of tumors in the hind limb field of the embryonic chick and the developmental response of the lumbosacral nervous system.Anat Rec102:
369–390,
1948
4.
ChangM. J. W.WebbT. E.KoestnerA.:
Distribution of 06-methylguanine in rat DNA following pretreatment in vivo with methylnitrosourea.Cancer Lett6:
123–127,
1979
5.
ConnollyJ. L.GreeneL. A.ViscarelloR. R.RileyW. D.:
Rapid sequential changes in surface morphology of PC 12 pheochromocytoma cells in response to nerve growth factor.J Cell Biol82:
820–827,
1979
6.
DavisonE. H.ButtenR. J.:
Molecular aspects of gene regulation in animal cells.Cancer Res34:
2034–2043,
1974
7.
DenlingerR. H.SwenbergJ. A.KoestnerA.WechslerW.:
Differential effect of immunosuppression on the induction of nervous system and bladder tumors by n-methyl n-nitrosourea.JNCI50:
87–93,
1973
8.
DichterM. A.TischlerA. S.GreeneL. A.:
Nerve growth factor-induced increase in electrical excitability and acetylcholine sensitivity of a rat pheochromocytoma cell line.Nature268:
501–504,
1977
9.
GothR.RajewskyM.:
Persistence of 06-ethylguanine in rat brain DNA: Correlation with nervous system-specific carcinogenesis by ethylnitrosourea.Proc Natl Acad Sci (USA)71:
639–643,
1974
10.
GreeneLA.ShooterE. M.:
The nerve growth factor: Biochemistry, synthesis, and mechanism of action.Annu Rev Neurosci3:
353–402,
1980
11.
GreeneL. A.TischlerA. S.:
Establishment of a non-adrenergic clonal cell line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.Proc Natl Acad Sci (USA)73:
2424–2428,
1976
12.
GuroffG.DickensG.EndD.:
The induction of ornithine decarboxylase by nerve growth factor and epidermal growth factor in PC 12 cells.J Neurochem37:
342–349,
1981
13.
HollidayR.PughJ. E.:
DNA modification mechanisms and gene activation during development.Science187:
226–232,
1975
14.
KoestnerA.SwenbergJ. A.DenlingerR. H.:
Host factors affecting perinatal carcinogenesis by resorptive alkylnitrosoureas in rats.Natl Cancer Inst Monogr51:
211–217,
1979
15.
KoestnerA.SwenbergJ. A.WechslerW.:
Transplacental production with ethylnitrosourea of neoplasms of the nervous system in Sprague-Dawley rats.Am J Pathol63:
37–56,
1971
16.
KoestnerA.SwenbergJ. A.WechslerW.:
Experimental tumors of the nervous system induced by resorptive n-nitrosourea compounds.Prog Exp Tumor Res17:
9–30,
1972
17.
Levi-MontalciniR.:
The morphological effects of immunosympathectomy. In:
Immunosympathectomy,
ed.
SteinerG.SchonbaumE.,
pp. 55–78.
Elsevier/North-Holland,
1972
Levi-MontalciniR.HamburgerV.:
Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo.J Exp Zool116:
321–362,
1951
20.
Levi-MontalciniR.HamburgerV.:
A diffusable agent of mouse sarcoma, producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embryo.J Exp Zool123:
233–288,
1953
21.
McGuireJ. C.GreeneL. A.:
Rapid stimulation by nerve growth factor of amino acid uptake by clonal PC 12 pheochromocytoma cells.J Biol Chem254:
3362–3367,
1979
MorantzR. A.ShainW.CraviotoH.:
Immune surveillance and tumors of the nervous system.J Neurosurg49:
84–92,
1978
24.
Perez-PoloJ. R.ShooterE. M.:
The preparation and properties of nerve growth factor protein at alkaline pH.Neurobiology (Copenh)5:
329–338,
1975
25.
ReynoldsC. P.Perez-PoloJ. R.:
Induction of neurite outgrowth in the IMR-32 human neuroblastoma cell line by nerve growth factor.J Neurosci Res6:
319–325,
1981
26.
SwenbergJ. A.ClendenonN.DenlingerR.GordonW. A.:
Sequential development of ethylnitrosourea-induced neurinomas: Morphology, biochemistry, and transplantability.JNCI55:
147–152,
1975
27.
SwenbergJ. A.KoestnerA.WechslerW.DenlingerR. H.:
Quantitative aspects of transplacental tumor induction with ethylnitrosourea in rats.Cancer Res32:
2656–2660,
1972
28.
SwenbergJ.WechslerW.KoestnerA.:
The sequential development of transplacentally-induced neuroectodermal tumors.J Neuropathol Exp Neurol31:
202–203,
1972
29.
TischlerA. S.DelellisR. A.BialesB.NunnemacherG.CarabbaV.WolfeH. J.:
Nerve growth factor-induced neurite outgrowth from normal human chromaffin cells.Lab Invest43:
399–409,
1980
30.
VaronS. S.:
Nerve growth factor and its mode of action.Exp Neurol43:
75–92,
1975
31.
VaronS.NomuraJ.Perez-PoloJ. R.ShooterE. M.:
The isolation and assay of the nerve growth factor proteins. In:
Methods in Neurochemistry,
ed.
FriedR.,
pp. 203–209.
Marcel-Decker, Inc.,
New York,
1972
VinoresS. A.KoestnerA.:
The effect of nerve growth factor on undifferentiated glioma cells.Cancer Lett10:
309–318,
1980
34.
VinoresS. A.KoestnerA.:
Reduction of ethylnitrosourea-induced neoplastic proliferation in rat trigeminal nerves by nerve growth factor.Cancer Res42:
1038–1040,
1982
35.
VinoresS. A.MarangosP. J.ParmaA. M.GuroffG.:
Increased levels of neuron-specific enolase in PC12 pheochromocytoma cells as a result of nerve growth factor treatment.J Neurochem37:
597–600,
1981
36.
VinoresS. A.Perez-poloJ. R.:
The effect of nerve growth factor and antibodies to nerve growth factor on ethylnitrosourea carcinogenesis in mice.J Cancer Res Clin Oncol98:
59–63,
1980
37.
VinoresS. A.Perez-PoloJ. R.:
Role of nerve growth factor in ethylnitrosourea -induced neural carcinogenesis.J Neurosci Res5:
351–361,
1980
38.
VinoresS. A.Perez-PoloJ. R.:
Nerve growth factor and neural oncology.J Neurosci Res9:
81–100,
1983
