Cyclophosphamide: effects of paternal exposure on the brain chemistry of the F1 progeny.

Abstract

The effects of acute and chronic cyclophosphamide (CP) exposure to male rats on several neurotransmitter enzymes have been examined in various brain regions of the F1 progeny at 90 d old. The acute postmeiotic CP exposure to male rats induced significant biphasic changes in the choline acetyltransferase (ChAT) activity in various brain regions of F1 progeny; significant decreases in the cerebellar acetylcholinesterase (AChE) activity of the male (47%) and the female (14%) F1 progeny, and moderate decrease (26%) in the hippocampal AChE activity in the female F1 progeny; and a moderate increase (29%) in the temporo-cortical glutamic acid decarboxylase (GAD) activity of the female F1 rats. The chronic CP-exposed male rats resulted in a slight but significant decrease (16%) in the temporo-cortical ChAT activity in the female F1 progeny; a marked increase (51%) in the hypothalamic AChE activity in the male F1 progeny; and a marked decrease (32%) in cerebellar GAD activity and a slight increase (13%) in the striatal GAD activity in the female F1 progeny. These enzymatic changes in the adult brain of F1 progeny of CP-treated males may be associated with the behavioral abnormalities observed previously. Results suggest that these neurochemical parameters may be useful markers for analysis of the potential neurotoxicity of CP.