Karyometric, cytophotometric and histoenzymatic studies on neuroglia of rats treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU/Lomoustine)

Abstract

CCNU is a cytostatic drug, a nitrosourea derivative, used--among others--in therapy of tumors of the central nervous system. Even if the drug is regarded safe for central and peripheral nervous systems, a possibility of harmful effects of CCNU on the central nervous system should be examined caused by the affinity of all nitrosourea derivatives to lipids. This has prompted us to study the drug effect on neuroglia cells in corpus callosum and gyrus cinguli. The drug was administered to rats by the intragastric route in four doses--one dose a week. Three doses of 2.5 mg each were followed by one dose of 5 mg. Some brains were isolated for the studies, and paraffin sections were prepared for karyometric as well as cytophotometric studies and for section staining according to Nissl and Klüver-Barrer techniques 8 days after the last dosage. Brains of other experimental rats served for preparing cryostat sections for demonstration of phosphatase and esterase activities. The studies, conducted after CCNU administration, documented a significant decrease in size of oligodendroglia nuclei and an increase in size of astroglia nuclei. DNA content of neuroglia nuclei was markedly decreased. Histoenzymatic changes in experimental animals were not very pronounced and included a slight increase in TPPase and nonspecific esterase activities as well as a decrease in ATPase activity. Despite the changes in neuroglia cells no damage to corpus callosum myelin sheaths was observed.