Antimitotic drugs in the male rat. Behavioral abnormalities in the second generation

The second generation descended from rats treated either with cyclophosphamide alone or with both cyclophosphamide and vinblastine were investigated. As in the first generation, the offspring were evaluated for mean litter size, sex ratio, frequency of gross external malformations and, within the first 4 months of life, growth and mortality. When they reached adulthood, between 12 and 16 weeks of age, the offspring were also tested for spontaneous activity and learning capacity. At birth, the progeny of the treated grandfathers did not show malformations or any other obvious disorder. However, when compared with the control population, the experimental animals showed significantly decreased success rates in a learning task, whatever the learning performance of their parents. Furthermore, decreased spontaneous activity was observed in the male subjects from unsuccessful parents. The similarities between the anomalies found in the first and the second generations argue for the induction of mutations by antimitotic drugs. This hypothesis and the subtle differences between generations and between sexes are discussed.