Transmission of the effects of paternal pre-fertilization exposure to a genotoxic drug being manifested in the F1 progeny is well established using the traditional rodent dominant lethal protocol . More recently, the induction of genotoxic effects in the F1 progeny following chronic paternal exposure prior to fertilization has been described in rats using behavioral testing as an endpoint . In our initial study, male F344 adult rats were treated chronically with 10 mg/kg cyclophosphamide (CP) or saline for 5 weeks (5 days of daily treatment and 2 days of rest). The present study describes the behavior of progeny whose fathers were treated with a single intraperitoneal injection of 10 mg/kg CP and mated at different times post-injection. This design showed that post-meiotic germ cells are the most sensitive to the effects of CP as seen by behavioral testing of the F1 progeny.
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