[A novel rat aplastic anemia model induced by 5-fluorouracil combined with busulfan].
OBJECTIVE
To develop an aplastic anemia model with hematopoietic stem cell failure in rats.


METHODS
Normal Wistar rats were injected i.p. with 5-fluorouracil and 5 days later p.o. by busulfan once a week for 3 times. A 5-FU alone group and a busulfan alone group were as control. The parameters tested indices were as following: incidence and mortality of aplastic anemia rats, blood picture, bone marrow nucleated cell count, CFU-GM of bone marrow cells and histology of hematopoietic organs.


RESULTS
In the 5-FU plus busulfan group, the incidence of acute aplastic anemia was 82.0% (40/49 rats), the average survival time was (30.0 +/- 6.5) days. The remained 9 rats developed chronic aplastic anemia (18.0%). The total incidence of aplastic anemia was 100%, and the mortality was 98%. The blood cells count of the aplastic anemia rats was gradually reduced to a level of half the premedications and no CFU-GM was detected, and the patho-morphological examination showed that the bone marrow was replaced by fat cells, and the lymphoid tissue of spleen, thymus and lymph-nodes were remarkably atrophied without extra-medullary hematopoiesis. The control group (5-FU treated) developed a transient hematopoiesis suppression, and recovered rapidly to normal. Three of 12 rats in the busulfan treated group developed aplastic anemia.


CONCLUSIONS
5-FU combined with busulfan could impair the hematopoietic stem cells and resulted in an irreversible aplastic anemia in rats, making a rat aplastic anemia model with hematopoietic stem cell failure.
Zhao
J
J
The State Key Lab of Experimental Hematology, Institute of Hematology, CAMS & PUMC, Tianjin, 300020, China.
Chu
J
J
Ding
S
S
Xu
S
S
Liu
A
A
Wang
S
S
D000741:Anemia, Aplastic / Q000097:blood / Q000139:chemically induced* / Q000401:mortality; D000818:Animals; D001772:Blood Cell Count; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007274:Injections, Intraperitoneal; D051381:Rats; D017208:Rats, Wistar
D002066:Busulfan; D005472:Fluorouracil