Serum 'uracil plus uridine' levels in normal subjects and their possible significance.

A microbiological method for the assay of uracil is described. The growth of the test organism is supported by uracil and also by uridine but not by uridylic acid. The method therefore measures uracil and uridine together. The ;uracil + uridine' level, expressed as uracil, has been measured in blood from 144 normal subjects ranging in age from cord blood to the eighth decade. The mean level of 22 mu mol/l (0.25 mg%) in cord blood decreases to 15 mumol/l (0.17 mg%) in adults over the age of 20. There is no difference between the sexes. Uracil is of interest because (a) it is a constituent base of RNA, (b) it is the precursor of two of the bases thymine and cytosine that enter into the composition of DNA, and (c) under certain circumstances it has mutagenic properties. The last is dependent upon the existence of two tautomeric forms of uracil, the common keto form which pairs normally with adenine and the rare enol form which pairs with guanine. A mistake in base pairing which allows uracil in its enol form to enter the DNA molecule and pair with guanine can result in a G = C --> A = T base transition in the DNA molecule. The molecular mechanism involved as well as the possible bearing on somatic mutation are discussed.