Possible mechanisms for the genesis of common chromosome abnormalities, including isochromosomes and the philadelphia chromosome.

SUMMARY In a continuing search for unique karyotypic changes in human leukemia and cancer, investigators have encoun tered a number of patients in whom partial trisomy and longitudinal duplication of some chromosomal regions, both involving especially the long arm of Chromosome 1, and isochromosomes were present. These abnormalities were also observed by us in human phytohemagglutinin stimulated lymphocyte metaphases at the second mitosis following exposure to Mitomycin C, which induces a num ber of chromosome aberrations, i.e., breaks and ex changes. The occurrence of these abnormalities, i.e., par tial trisomy and longitudinal duplication of chromosomes, could be attributed primarily to the manner of segregation of exchange quadriradials. The finding of isochromosomes at the second metaphase and the presence of adjacent homologous exchanges at centromeric regions in the first metaphase after treatment with Mitomycin suggest the pos sibility of the production of isochromosomes through ex changes, as well as through â€oemisdivision†• of the centro mere. In addition to the possible mechanisms underlying the genesis of chromosome abnormalities mentioned above and frequently observed in human leukemia and cancer, a possible mechanism for the genesis of the Philadelphia chromosome is discussed on the basis of chromosomal findings in chronic myelocytic leukemia and changes in duced by Mitomycin C.