Purine salvage in vitro by mouse tooth germs exposed to mycophenolic acid

Abstract

Mycophenolic acid (MPA), an oncolytic agent produced by Penicillium stoloniferum, inhibits the conversion of inosine monophosphate to guanosine monophosphate. Molar tooth germs prepared from 15- and 16-day old C57BL/6J embryos were maintained on agar-solidified McCoy's 5a medium (modified), supplemented with glutamine, antibiotics and fetal bovine serum, in 5 per cent CO 2 95 per cent air. At a concentration of 44 μM, MPA severely inhibited growth and development of the germs expressed as abnormal folding of the dentine-enamel junction, disorientation of pre-ameloblasts, retardation of growth, cell death and failure of 2nd molar germs to develop. These effects, after 4 days in culture, contrasted with larger explants produced during the same period on control medium, exhibiting normally developing 1st and 2nd molar germs. Explants transferred to control medium did not recover over a 4-day period. When the explants were grown on medium containing MPA and guanine the effects of MPA were prevented. The results suggest that: (a) tooth germ development depends on de novo guanine nucleotide synthesis and (b) salvage as well as de novo guanine nucleotide biosynthetic enzymes can function in normal tooth development.