Cyclophosphamide in the male rat: cerebral biochemical changes in progeny

Adult male Wistar rats were treated with cyclophosphamide either alone or with both cyclophosphamide and vinblastine. They were then mated with virgin non-treated females. Examination of their offspring showed an increased post-natal mortality rate; and diminished learning capacity and spontaneous activity in the adults. These disorders were also found in the second generation, resulting from mating between animals of the first generation. Biochemical analyses of the brains of the offspring of treated males in the first and second generations showed a diminished activity of hippocampal choline acetyl-transferase. Moreover, the second generation showed a diminution of fronto-parietal cortex norepinephrine. These biochemical results may correspond to the observed behavioral deficits. Furthermore, by studying experimental mutation, they add to our knowledge of the consequences of certain cytostatic treatments.