ELSEVIER Mutation Research 316 (1994) 1-7 MUTATION RESEARCH DNAging The frequency of micronuclei with X chromosome increases with age in human females Florence Richard *, Martine Muleris, Bernard Dutrillaux URA 620 CNRS, Institut Curie, Section de Biologie, 26 rue d'Ulm, 75231 Paris Cedex 05, France (Received 29 June 1993) (Revision received 26 August 1993) (Accepted 31 August 1993) Abstract The rate of micronuclei counted on lymphocyte cultures from five healthy female donors, 27-80 years old, increased with age. Using pXBR1 probe, specific for the alphoid DNA of the X chromosome, the presence of this chromosome was investigated by FISH (fluorescence in situ hybridization) in both micronuclei and metaphases. Both X aneuploidy and frequency of X chromosome per micronuclei increased with age. However, this overinvolvement of X chromosome was not sufficient to explain the overall increase of micronuclei with age, suggesting that autosomes are also involved. Thus, the higher increase of X than autosome aneuploidy in lymphocytes may result from both an excess of X chromosome losses and a better survival of cells with a monosomy X. Key words: X chromosome; Micronuclei; Ageing; Lymphocytes; Human 1. Introduction Several studies suggested that aneuploidy in lymphocytes from healthy donors is related to age and sex (Jacobs and Court Brown, 1961; Jarvik et al., 1976; Fitzgerald and McEwan, 1977; Martin et al., 1980; Ford and Russel, 1985; Nowinski et al., 1990). The difference was shown to depend on the increase of sex chromosome losses, the late replicating X of females being more fre- quently involved than the Y chromosome of males * Corresponding author. (Fitzgerald et al., 1975; Galloway and Buckton, 1978; Abruzzo et al., 1985; Richard et al., 1993). Studies on micronuclei provided similar obser- vations: they increase with age and are more frequent in females than in males (Scarfi et al., 1990; Migliore et al., 1991; H6gstedt et al., 1991; Au et al., 1991; Tomanin et al., 1991). In spite of this similarity, there was no demonstration that X chromosome aneuploidy and micronucleus for- mation are closely related. To test this possibility, we developed a fluorescence in situ hybridization (FISH) study, comparing the involvement of X chromosome and autosomes in mieronuclei of female lymphocytes. 0921-8734/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0921-8734(93)E0007-Z