Histoenzymatic, karyometric, and DNA cytophotometric studies on rat neuroglia following administration of BCNU (Carmustine)

Abstract

BCNU is a nitrosourea derivative applied in anti-neoplastic therapy. As a result of conversion under in vivo-conditions, products of alkylating properties are formed which derrange DNA metabolism, and products of carbamylating activity which disturb protein metabolism. Studies on BCNU neurotoxicity were performed on 20 adult rats of Wistar strain which were given the compound intraperitoneally, in doses corresponding to those used for tumour treatment in humans. Material for estimating unfavorable effects of the drug on central nervous system involved brains, the sections of which were subjected to histoenzymatic reactions and stained according to FEULGEN for karyometric studies and DNA cytophotometry. Size and shape estimates for nuclei of the cells and their DNA content were obtained using Morphoquant automatic microscopic image analyzer (VEB Carl Zeiss, Jena) and compared to those of neuroglia of control animals, given no drug. Multiple intraperitoneal injections of BCNU induced distinct histoenzymatic, karyometric, and cytophotometric changes in oligodendroglia and astroglia. In oligodendroglia, lowered NsE and AcP activities and augmented TPPase activity were noted while in astroglia decreased activity of the former 2 enzymes was associated with an augmented ATPase activity. In karyometric studies, significant decrease in the size of astroglia and in DNA extinction was noted. No karyometric or cytophotometric alterations were noted in oligodendroglia nuclei. Results of the presented studies may indicate primary injury to vascular walls and secondary damage to neuroglia.