Chromosome-specific induction of micronuclei and chromosomal aberrations by mitomycin C: Involvement of human chromosomes 9, 1 and 16

Mutat Res Genet Toxicol Environ Mutagen. 2024 May-Jun:896:503753. doi: 10.1016/j.mrgentox.2024.503753. Epub 2024 Mar 29.


Cytogenetic studies have shown that human chromosomes 1, 9, and 16, with a large heterochromatic region of highly methylated classical satellite DNA, are prone to induction of chromatid breaks and interchanges by mitomycin C (MMC). A couple of studies have indicated that material from chromosome 9, and possibly also from chromosomes 1 and 16, are preferentially micronucleated by MMC. Here, we further examined the chromosome-specific induction of micronuclei (MN; with and without cytochalasin B) and chromosomal aberrations (CAs) by MMC. Cultures of isolated human lymphocytes from two male donors were treated (at 48 h of culture, for 24 h) with MMC (500 ng/ml), and the induced MN were examined by a pancentromeric DNA probe and paint probe for chromosome 9, and by paint probes for chromosomes 1 and 16. MMC increased the total frequency of MN by 6-8-fold but the frequency of chromosome 9 -positive (9+) MN by 29-30-fold and the frequency of chromosome 1 -positive (1+) MN and chromosome 16 -positive (16+) MN by 12-16-fold and 10-17-fold, respectively. After treatment with MMC, 34-47 % of all MN were 9+, 17-20 % 1+, and 3-4 % 16+. The majority (94-96 %) of the 9+ MN contained no centromere and thus harboured acentric fragments. When MMC-induced CAs aberrations were characterized by using the pancentromeric DNA probe and probes for the classical satellite region and long- and short- arm telomeres of chromosome 9, a high proportion of chromosomal breaks (31 %) and interchanges (41 %) concerned chromosome 9. In 83 % of cases, the breakpoint in chromosome 9 was just below the region (9cen-q12) labelled by the classical satellite probe. Our results indicate that MMC specifically induces MN harbouring fragments of chromosome 9, 1, and 16. CAs of chromosome 9 are highly overrepresented in metaphases of MMC-treated lymphocytes. The preferential breakpoint is below the region 9q12.

Keywords: Chromosomal aberrations; Chromosome 1; Chromosome 16; Chromosome 9; Micronucleus; Mitomycin C.

MeSH terms

  • Adult
  • Cells, Cultured
  • Chromosome Aberrations* / chemically induced
  • Chromosome Aberrations* / drug effects
  • Chromosomes, Human, Pair 1* / genetics
  • Chromosomes, Human, Pair 16* / genetics
  • Chromosomes, Human, Pair 9* / genetics
  • Cytochalasin B / pharmacology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Micronuclei, Chromosome-Defective* / chemically induced
  • Micronuclei, Chromosome-Defective* / drug effects
  • Micronucleus Tests
  • Mitomycin* / pharmacology
  • Mitomycin* / toxicity


  • Mitomycin
  • Cytochalasin B