No abstract

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.

No abstract

Several abnormalities, such as postnatal deaths and behavioral impairments, have been previously reported in the progeny of male rats exposed to the cytostatic drug cyclophosphamide 60 days prior to mating. The anomalies were transmitted to the second generation (F2). The present results concern the third generation. Two experimental groups have been studied: a hybrid group, resulting from crosses between control subjects and either experimental F2 males or females, and a nonhybrid group, obtained by mating experimental F2 subjects together. Significant abnormalities were found in all experimental groups, whether the F2 subjects were male or female. F2 females had smaller litters whether they were mated with control or experimental males. Body weight was significantly increased in both hybrid and nonhybrid males. Increased postnatal mortality and learning deficit were also observed in the hybrid group. Such complex phenotypic changes confirm that frequent mutations probably have been inherited from the treated males but also suggest that genetic rearrangements have occurred from one generation to the next.