Preleukemic proliferative changes in murine bone marrow after single and multiple 7,12-dimethylbenz(a)anthracene (DMBA)-applications.

The effect of a leukemia-inducing treatment on early changes in kinetic parameters of murine bone marrow cells were investigated. Mice were treated i.p. one, four and eight times at biweekly intervals with 1 mg DMBA. Up to nine weeks after the last injection, CFU-S number, proliferation ability of bone marrow cells (PF), cell doubling time (td) and the compartment ratio (CR) were measured. Following multiple DMBA injections, CFU-S number and PF were decreased whereas CR and td increased, thus indicating persisting stem cell injury and proliferative compensation in the hemopoietic amplification compartment. A single DMBA injection had no effect. It is concluded that a first DMBA injection induces cytotoxic (and genotoxic) damage in the bone marrow leading simultaneously to a strong proliferation stimulus and a hindered proliferation ability of HSC, some of which will be predisposed for further mutagenic treatment. The following DMBA injections meet strongly proliferating HSCs, thus enhancing the probability for the loss of proliferation control/terminal differentiation.