Recovery patterns of rat hemopoietic stem cells between pulse doses of 7,12-dimethylbenz(a)anthracene (DMBA) applied in a leukemogenic regimen.
Male Wistar rats received repeated pulse doses of 7,12-dimethylbenz(a)anthracene (DMBA), known to elicit myelodysplasia followed by acute, mostly erythroblastic, leukemia at 10-day intervals. The recovery of spleen colony forming hemopoietic stem cells (CFU-s) surviving the cytocidal action of DMBA was examined between pulses. Recovery after a pulse of 35 mg/kg body weight varied with the organ source of the CFU-s (femoral bone marrow or spleen) and the number of preceding DMBA pulses. After a single DMBA pulse bone marrow CFU-s initially recovered faster than reported for normal bone marrow CFU-s transplanted into chemically conditioned rats. But recovery was followed by regeneration arrest. Population doubling times of marrow CFU-s increased with the number of DMBA pulses. Recovery of splenic CFU-s was slower after a single DMBA pulse than reported for normal spleen CFU-s transplanted into chemically conditioned rats. The CFU-s population doubling times were not significantly different after a single or five DMBA pulses. After three pulses, however, recovery of splenic CFU-s was exceedingly slow until day 5 and subsequently accelerated, but was still slower than after one or five pulses. In the spleen CFU-s recovery was always accompanied by regeneration of total cell numbers with a preference for erythroid regeneration. In the bone marrow this was the case after three DMBA pulses only.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002869:Chromosome Aberrations; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007942:Leukemia, Experimental / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000187:drug effects
D015127:9,10-Dimethyl-1,2-benzanthracene