Guanine salvage by organ cultures of mouse tooth germs.

Abstract

The effect of mycophenolic acid (MPA) which inhibits the biosynthesis of guanosine monophosphate (GMP) in organ cultures of mouse tooth germs can be partially counteracted by adding guanine to the MPA cultures. This may be due to salvaging guanine by the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT), or to competition for a common membrane carrier involved in mediated transport of both guanine and hypoxanthine in normal biosynthesis and also of MPA. Experiments were carried out to compare the effect of either hypoxanthine or guanine on the MPA-caused inhibition. While addition of guanine to the MPA cultures (MPAG) supports growth equal to controls and development of dental-enamel junction (DEJ) to a level intermediate between control and MPA the addition of hypoxanthine (MPAHX) supports growth and DEJ development not better than MPA. This indicates that guanine is salvaged by HGPRT to GMP while hypoxanthine, salvaged to inosinic acid (inosinic monophosphate, IMP) is ineffective because the MPA inhibition is on the pathway from IMP to GMP.