Cyclophosphamide induced polydactyly in mice: understanding of underlying mechanism

Polydactyly with 6 or 7 digits bilaterally, or in all the four limbs at a time in certain cases was the principal finding amongst limb malformations in mice fetuses exposed to cyclophos-phamide in the dose of 10 mg /kg body weight on day 11 of gestation. Duplication of great toe was the most dominant. Augmentation of apoptosis by cyclophosphamide resulting in excessive programmed cell death in additional interdigital zones due to altered induction from apical ectodermal ridge (AER) with subsiquent early and fast destruction of AER and mesoderm deep to it were suggested as the probable mechanisms. Bilateral manifestation or involvement of all the four paws in multiple cases suggested , homogeneous effect of cyclo-phosphamide on the process of differentiation i.e. administration of critical dose at critical period of differentiation of toes.