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Cyclophosphamide in the Fo male rat: physical and behavioral changes in three successive adult generations

Cyclophosphamide in the Fo male rat: physical and behavioral changes in three successive adult generations

Mutation Research, Fundamental and Molecular Mechanisms of Mutagenesis 229(2): 189-198

Three-month-old [male][male] were treated with cyclophosphamide, mated after 60 days (equivalent to 1 spermatogenic cycle) or 100 days (2 spermatogenic cycles), and their offspring evaluated for learning ability of a conditioned avoidance response. The learning capacity of [male] offspring from treated [male][male] mated at 60 days was significantly lower than that of control offspring (from untreated sires). Activity of hippocampal choline acetyltransferase (the enzyme involved in the memory process) of [male] offspring was also lower (P<0.02) than that of control [male][male]. Offspring of treated [male][male] were mated randomly and the offspring in the next generation (F2T) were compared with those (F2C) derived from the control population. The learning ability of [male][male] with treated grandsires was significantly lower than that of control [male][male], but no difference was seen in [female][female]. F2T X F2T, F2T X F2C and F2C X F2C matings were carried out to derive F3T, F3H and F3C resp. The F3H and F3T groups exhibited anomalies in litter size and body weight, but only slight differences in learning ability or enzyme activity. The results indicated that cyclophosphamide induced transmissible mutations affecting learning ability.

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Accession: 001790958

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PMID: 2320031

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