A comparative study on the effects of 5-fluorouracil on glycosaminoglycan synthesis during palate development in...

A comparative study was undertaken to investigate the effects of 5-fluorouracil (FU) on glycosaminoglycans (GAG) synthesis during morphogenesis of the secondary palate in birds (where, unlike mammals, palate morphogenesis begins in a horizontal direction ad initium and lacks mammalian-type shelf reorientation) and mammal. Previous studies have shown that FU induces cleft palate in both birds and mammals. Air sacs of quail eggs were injected with 100 micrograms FU in 0.1 ml saline or 0.1 ml saline only. Hamsters were given intramuscular injection of 81 mg/kg FU in 1 ml saline or 1 ml saline only. Total GAG synthesis was measured by incorporation of 3H-glucosamine. Sulfated and non-sulfated GAGs were identified by Alcian Blue histochemistry combined with the use of GAG-degrading enzymes. The results indicated that a continuous synthesis of GAG at a steady rate was associated with normal palate morphogenesis in both quail and hamster. The amount of GAG synthesized in hamster palate was four-fold higher than in quail palate. In contrast to the developing hamster palate where the predominant GAG was hyaluronate, the major GAGs present during quail palate development were sulfated and were concentrated on the nasal side. FU treatment did not affect the rate of GAG synthesis in the developing palate of quail. In contrast, FU administration altered the rates of GAG synthesis, and affected hyaluronate accumulation, during palate morphogenesis in hamster.(ABSTRACT TRUNCATED AT 250 WORDS)