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Skeletal malformations of forelimbs of rat fetuses caused by maternal administration of cyclophosphamide during pregnancy.

There are numerous reports on artificial induction of limb anomalies in different laboratory animals by a variety of treatments during gestation e.g. X-irradiation, hypoxia, vitamin A excess and deficiency, antitumour substances, nutritional deficiencies, enzyme inhibitors, alkaloids, antihistamines, thalidomide, etc. (for references, see Singh, Sanyal & Singh, 1973). Cyclophosphamide, a recently synthesized potent cytostatic agent belonging to the alkylating group (nitrogen mustard), has been extensively used in various types of cancer, especially in acute childhood leukaemia, because of its low toxicity and high therapeutic index (for references, see Chaube, Kury & Murphy, 1967). Congenital anomalies, probably induced by cyclophosphamide, have been reported in a human fetus (Greenberg & Tanaka, 1964). This drug has been shown to be teratogenic in several laboratory animals e.g. chicks, rats, rabbits and mice (for references, see Singh, 1971). The major action of cyclophosphamide seems to be an inhibition of deoxyribonucleic acid (DNA) synthesis especially affecting mesenchymal tissue (Chaube et al. 1967; Singh, Tuli & Gupta, 1971). Limb anomalies in rat fetuses are found to be most frequent when cyclophosphamide is given during 12th-14th day of gestation (Singh & Sanyal, 1972). The present report communicates the skeletal malformations of the forelimbs of rat fetuses induced by cyclophosphamide administration during the 12th-14th day of gestation.