Alterations of glycosaminoglycans synthesized by chick embryo cartilage treated with 6-aminonicotinamide.

Treatment of day-4 chick embryos with 6-aminonicotinamide (6-AN) impairs limb chondrogenesis and produce micromelia. However, treatment of day-10 chick embryos with 6-AN does not produce micromelia. In the present study, the glycosaminoglycan (GAG) biosynthesis in the cartilage isolated from the day-10 chick embryos treated with 6-AN in vitro and in the cartilage from the day-11 chick embryos treated with 6-AN in ovo at day-10 was examined. In the epiphyseal cartilage treated in vitro, the radioactivity incorporated into the GAG fraction was significantly decreased and the 35S/3H ration in the GAG fraction and the molecular size of GAG chain were also decreased. However, the percent distribution of ΔDi-OS was almost unchanged. In the epiphyseal and diaphyseal cartilage treated in ovo at day-10, the alteration in GAG biosynthesis was not observed except the reduction of the molecular size of GAG in epiphyseal cartilage. Furthermore, the biosynthetic activity of GAG in the process of recovery/repair was also examined using the micromelial cartilage isolated from day-11 chick embryos given 6-AN in ovo at day-4. In the diaphyseal cartilage, the radioactivity incorporated into the GAG fraction and the 35S/3H ratio were increased, whereas the percent distribution of ΔDi-OS was almost unchanged. These results indicate that treatment of day-4 chick embryos with 6-AN produces the rebound phenomena in the diaphyseal cartilage isolated at day-11. In the present study, it has become clear that 6-AN directly impairs GAG biosynthesis in epiphyseal cartilage and that the effects of 6-AN on isolated cartilage differ from the effects of 6-AN on limb mesoderm in ovo. Thus, the defects induced by 6-AN in isolated cartilage cannot be conceived of as the cause of the bone malformation asserted by Seegmiller et al.