SUGGESTIONS CONCERNING THE RELATIONSHIP BETWEEN MUTANT FREQUENCY AND MUTATION-RATE AT THE HPRT LOCUS IN HUMAN PERIPHERAL T-LYMPHOCYTES

Mutant frequency is defined as the proportion of mutant cells in a pop ulation and is readily estimated. It should be distinguished from muta tion rate, which relates to the rate at which mutation events arise, a nd is generally expressed as events per cell division. Since one mutat ion event may give rise to one or many mutant cells, depending on the generation in which it has arisen, the relationship of mutant frequenc y to the underlying mutation rate is complex. A large number of estima tes of mutant frequency at the hprt locus in human lymphocytes are ava ilable, from our two laboratories among others, From our two extensive data sets, we have determined median hprt mutant frequencies of diffe rent age groups and used the method of Lea and Coulson (J. Genet., 49, 1949, 264-285) to attempt to estimate the underlying mutation rate at this locus. It is in principle possible to obtain estimates of mutati on rate from the mutant frequency in newborns, from the increase in mu tant frequency with age, and from the difference between the upper and lower quartile mutant frequencies. We discuss reasons for the discrep ancies between these estimates and argue that the best estimate can pr obably be obtained from the increase in mutant frequency with age. We arrive at an estimate of mutation rate to 6-thioguanine resistance at the hprt locus of about 5 X 10(-7) mutation events per nominal cell di vision.