The effects of age and lifestyle factors on the accumulation of cytogenetic damage as measured by chromosome painting.

摘要

Individual responses to the aging process are variable and are affected by genetic as well as environmental factors. Fluorescent in situ hybridization with whole chromosome probes ('chromosome painting') provides an efficient approach for detecting structural chromosome aberrations in human lymphocytes. This rapid and sensitive technique is an effective tool for quantifying chronic exposure to environmental agents which may result in an accumulation of cytogenetic damage with age. We have applied this technology to a normal, putatively unexposed, population to document the relationship between age and the accumulation of cytogenetic damage, as well as to establish a baseline frequency of stable aberrations. Using probes for chromosomes 1, 2 and 4 simultaneously, the equivalent of 1000 metaphases was scored for stable and unstable aberrations from each of 91 subjects ranging in age from newborns (umbilical cord bloods; n = 14) to adults aged 19 to 79 years. Each subject (or one parent of each newborn) completed an extensive questionnaire to identify possible lifestyle factors that may influence the frequency of cytogenetic damage. Our findings show a significant increase in stable aberrations (translocations and insertions) with age (p < 0.0001). We also observed age-related increases with dicentrics (p < 0.0001) and acentric fragments (p < 0.0001). Relative to the frequencies observed in cord bloods, the frequencies of stable aberrations, dicentrics, and acentric fragments in adults aged 50 and over were elevated 10.6-fold, 3.3-fold, and 2.9-fold, respectively. Nine variables other than age are significantly associated with the frequency of stable aberrations; these are: smoking (two variables), consumption of diet drinks and/or diet sweeteners (4 variables), exposure to asbestos or coal products (1 variable each), and having a previous major illness (1 variable). Newborns whose mothers smoked during pregnancy had a 1.5-fold increase in stable aberrations (p = 0.029). Repeat samples from a subset 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 aberrations show a greater accumulation with age than do unstable aberrations and suggest that lifestyle factors contribute to the accumulation of cytogenetic damage.