Spontaneous and spindle poison-induced micronuclei and chromosome non-disjunction in cytokinesis-blocked lymphocytes from two age groups of women.

Fluorescence in situ hybridization (FISH) was used to evaluate spontaneous and aneuploidogen-induced micronucleus frequencies and non-disjunction of chromosomes X and 8 in cultured binucleated lymphocytes of women of two age groups. Demecolcine and vincristine were used as model aneuploidogens to induce micronuclei and chromosome malsegregation. Four of the women were aged 22-26 (mean 24.3) years and four 47-50 (mean 49.0) years. Pancentromeric FISH was applied to micronuclei to identify chromosomes and double-color centromeric FISH, performed in binucleates of two young and two older women, was used to assess the involvement of chromosomes X and 8 in micronuclei and non-disjunction. It was confirmed that age increases micronucleus frequency. Micronuclei containing whole chromosomes predominated in older females. Age also enhanced micronuclei containing acentric chromosome fragments. The inclusion of chromosomes X and 8 in micronuclei was enhanced by age and chromosome X was generally overrepresented. Non-disjunction of chromosomes X and 8 also increased with age, chromosome X being the more sensitive. Treatment of lymphocytes with vincristine and demecolcine increased micronucleus frequency and malsegregation of chromosomes X and 8 in both age groups. Comparison of the estimated frequencies of micronucleation and non-disjunction for all human chromosomes showed that non-disjunction is the main type of chromosome malsegregation.