In vivo dose-response relationship in bone-marrow cells of mice treated with adriamycin

In bone-marrow cells of mice treated with a single dose of adriamycin and killed 6 h later, only chromatid-type aberrations were found. Animals studied 12 h after adriamycin injection showed chromatid- and chromosome-type aberrations, including Robertsonian centric fusions. The frequency of chromatid-type aberrations exhibited a direct-correlation with the dose in mice treated for 6 but not for 12 h. On the other hand, chromosome-type aberrations detected 12 h after injection were directly correlated with the dose of adriamycin. The induction in vivo of chromosome-type aberrations in mice studied 12 h after treatment suggests the existence of bone-marrow cell populations able to carry out 2 mitoses in this time lapse. The induction of Robertsonian fusions can be explained by the preferential induction of chromosomal lesions in pericentromeric heterochromatin followed by reunion of damaged segments of 2 chromosomes. Consequently, the metacentric-like chromosomes induced by adriamycin arise either from translocations involving entire chromosomes arms or from aberrations of the exchange type between 2 short arms of acrocentric chromosomes.