[Tumour induction by ethylnitrosourea in the central nervous system].
BACKGROUND
Experimental central nervous system (CNS) tumours have been proposed as a useful model for the study of oncogenesis, epiphenomena related to cancer and for the design of new therapeutic strategies.


METHODS
The administration of chemical substances is one of the most commonly-used methods to induce CNS neoplasms. N-ethyl-N-nitrosourea (ENU) belongs to the nitrosourea family, a wide group of alkylating agents that are able to induce brain tumours in litters after transplacentary administration at the 15th day of pregnancy. This nitrogenous urea compound has a high mutation inducibility affecting the expression of oncogenes such as p53, neu/erbB-2 and Ras. Prenatal exposition of Sprague Dawley rats to ENU induces intra-axial tumours of glial lineage and extra-axial malignant schwannomas. Although the precise mechanism of tumour induction is unclear, it is known to affect cell differentiation of primitive neuroepithelium from the subventricular plate generating oligodendrogliomas, astrocytomas, mixed gliomas or ependimomas.


CONCLUSIONS
The transplacentary administration of ENU induces the development of gliomas and schwannomas that are similar to those found in humans. Animal models are necessary and useful for further studies to get an early diagnosis and to establish correct therapeutic indications.
Bulnes-Sesma
S
S
Laboratorio de Neurociencias Clínicas y Experimentales (LANCE), Departamento de Neurociencias, Universidad del País Vasco, España.
Ullibarri-Ortiz de Zárate
N
N
Lafuente-Sánchez
J V
JV
D000477:Alkylating Agents / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001254:Astrocytoma / Q000139:chemically induced; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D016543:Central Nervous System Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004249:DNA Damage; D004806:Ependymoma / Q000139:chemically induced; D005038:Ethylnitrosourea / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005910:Glioma / Q000139:chemically induced; D008297:Male; D023421:Models, Animal; D016296:Mutagenesis / Q000187:drug effects; D009363:Neoplasm Proteins / Q000032:analysis; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009442:Neurilemmoma / Q000139:chemically induced; D009837:Oligodendroglioma / Q000139:chemically induced; D009857:Oncogenes / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000477:Alkylating Agents; D002273:Carcinogens; D009363:Neoplasm Proteins; D005038:Ethylnitrosourea