DETERMINATION OF HPRT MUTANT FREQUENCIES IN T-LYMPHOCYTES FROM A HEALTHY PEDIATRIC POPULATION - STATISTICAL COMPARISON BETWEEN NEWBORN, CHILDREN AND ADULT MUTANT FREQUENCIES, CLONING EFFICIENCY AND AGE

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning assay in a healthy pediatr ic population. Assays were performed on 49 subjects (29 males and 20 f emales) ranging in age from 0.08 to 15.2 years. A statistical analysis of the thioguanine-resistant (TG(r)) mutant frequency (MF), unselecte d cloning efficiency (CE) and age was performed using data obtained in this study and those previously obtained in our laboratory on 66 newb orn umbilical cord blood samples and 230 adult blood samples. For stat istical comparisons pediatric subjects were divided into 4 groups. Gro up I included cord blood samples (age 0 years); Group II were subjects between 0 and 5 years; Group III were between 6 and 11 years and Grou p IV were between 12 and 17 years. The In MF of Groups I and II were s ignificantly lower than Groups III and IV (p < 0.05). The mean In MF f or each of Groups I-IV was significantly lower than the adult value. T he cloning efficiency for Group I was significantly lower than that fo r Groups II-IV and adults. The relationships among the In MF, unselect ed CE and age were expressed by the equations: In (MF) = 0.945 - 2.453 CE (p < 0.001) and In (MF) = 0.114 + 0.063 age (p 0.004). The slope c oefficients for unselected CE and age were significantly different fro m adults (p < 0.05). Regression analysis of combined data from Groups I-IV and adults were performed using both age and unselected CE as wel l as terms to reflect differences in their relationships with In MF in adults and children. The results showed that the intercept and the ag e coefficients differ significantly for children and adults after adju stment for CE and yielded the following equations: In (MF) = 0.548 - 1 .676 CE + 0.075 age, (Groups I-IV) and In (MF) = 2.263 - 1.676 CE + 0. 014 age (adults). An alternative statistical model using In (age + 1), In (MF) = 0.381 - 1.767 CE + 0.673 In (age + 1), (p < 0.001), describ es the rapid increase in MF with age that levels off in late adolescen ce. These findings demonstrate the changing influence of age on mutant frequency in the pediatric population as compared to the adult popula tions. These studies also illustrate that the increase in backgrond so matic mutant frequencies at the hprt locus in T-lymphocytes is not lin ear from birth to adolescence and is significantly different from that seen in the adult population. This model can be used to determine the possible effects of genotoxic exposures in vivo on MF in children wit hin defined parameters such as age.