IMPACT OF AGE AND ENVIRONMENT ON SOMATIC MUTATION AT THE HPRT GENE OFT-LYMPHOCYTES IN HUMANS

Analysis of two human populations for dependence of somatic mutation o n age has revealed both similarities and differences. The studies perf ormed employed peripheral blood lymphocytes and measured the efficienc y with which these cells form clones in vitro (cloning efficiency, CE) and the frequency of cells with inactivating mutations of the hypoxan thine phosphoribosyltransferase gene (mutant frequency, MF). The peopl e studied were between 19 and 64 years of age. In one population, comp osed of 78 never smokers and 140 current smokers from the United State s (US), both CE and MF were dependent on age: CE declined with age(p = 0.005); MF increased 0.15 per 10(6) cells per year of age for nonsmok ers (p < 0.001) and at 1.3 times that rate for smokers (p = 0.01). In the second population, 80 people of unknown smoking status from Russia , the increase in MF per year was even greater, 2.5 times that of the US nonsmokers (p = 0.001) but the dependence of CE on age was the same as for the US population (p = 0.043). Because the increase of MF of t he Russians with age is 2-fold greater than that of the US smokers, th e intensity of smoking and/or other environmental exposures, or the su sceptibility to these exposures, must account for the difference in ag e dependent MF increase, not the proportion of Russians that are smoke rs. Differences in the lymphocyte subpopulations that survived the lon ger transit from Russia may have contributed to the observed differenc es in MF. However, overall, the mutant frequency results suggest that the Russians were chronically exposed to higher levels of agents that induce somatic mutation and that, on an age adjusted basis, the Russia population studied is at increased risk for health consequences from accumulated genetic damage.