THE EFFECTS OF AGE AND LIFE-STYLE FACTORS ON THE ACCUMULATION OF CYTOGENETIC DAMAGE AS MEASURED BY CHROMOSOME PAINTING

Individual responses to the aging process are variable and are affecte d by genetic as well as environmental factors. Fluorescent in situ hyb ridization with whole chromosome probes ('chromosome painting') provid es an efficient approach for detecting structural chromosome aberratio ns in human lymphocytes. This rapid and sensitive technique is an effe ctive tool for quantifying chronic exposure to environmental agents wh ich may result in an accumulation of cytogenetic damage with age. We h ave applied this technology to a normal, putatively unexposed, populat ion to document the relationship between age and the accumulation of c ytogenetic damage, as well as to establish a baseline frequency of sta ble aberrations. Using probes for chromosomes 1, 2 and 4 simultaneousl y, the equivalent of 1000 metaphases was scored for stable and unstabl e aberrations from each of 91 subjects ranging in age from newborns (u mbilical cord bloods; n = 14) to adults aged 19 to 79 years. Each subj ect (or one parent of each newborn) completed an extensive questionnai re to identify possible lifestyle factors that may influence the frequ ency of cytogenetic damage. Our findings show a significant increase i n stable aberrations (translocations and insertions) with age (p < 0.0 001). We also observed age-related increases with dicentrics (p < 0.00 01) and acentric fragments (p < 0.0001). Relative to the frequencies o bserved in cord bloods, the frequencies of stable aberrations, dicentr ics, and acentric fragments in adults aged 50 and over were elevated 1 0.6-fold, 3.3-fold, and 2.9-fold, respectively. Nine variables other t han age are significantly associated with the frequency of stable aber rations; these are: smoking (two variables), consumption of diet drink s and/or diet sweeteners (4 variables), exposure to asbestos or coal p roducts (1 variable each), and having a previous major illness (1 vari able). Newborns whose mothers smoked during pregnancy had a 1.5-fold i ncrease in stable aberrations (p = 0.029). Repeat samples from a subse t of the adults indicate that for most subjects there is little change in individual translocation frequencies over a period of two to three years. These results support the hypothesis that stable chromosome ab errations show a greater accumulation with age than do unstable aberra tions and suggest that lifestyle factors contribute to the accumulatio n of cytogenetic damage.