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6-mercaptopurine induced cleft palate in the hamster : morphological and cellular aspects Burdett, David Norman


A study on the pathogenesis of 6-mercaptopurine induced cleft palate was undertaken using light and electron microscopic, and enzyme acid phosphatase cytochemical techniques. Palatal development in control fetuses was observed in six stages at the gross level and five stages at the histological level. Between days 9:18 (9 days:18 hours) and 10:00 of gestation palatal primordia appeared from the roof of the oronasal cavity, and developed in the vertical direction until day 12:00 of gestation. Between days 12:00 and 13:00 of gestation the palatal shelves became horizontal and fused with one another. During closure the timely appearance of lysosomes was responsible for elimination of the intervening epithelia of the opposing palatal shelves through an intracellular process of autolysis. Gross observations showed that 6-mercaptopurine affected the vertical development of palatal shelves. In contrast to normal development, vertically developing palatal shelves on day 10:00 of gestation showed sublethal injury of the mesenchymal cells characterized by swelling of the perinuclear space and lysosomal development. Subsequently the epithelial cells were damaged, and the basal lamina fragmented and disappeared. The epithelial and mesenchymal cells communicated with one another. Eventually, however, the epithelial and mesenchymal cells recovered and the basal lamina re-established its continuity. It was concluded that sublethal injury of the mesenchymal and epithelial cells following 6-mercaptopurine treatment disturbed the controlled process of cytodifferentiation, and thus affected vertical development of the palatal shelves to develop a cleft palate.

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