Late effects of cyclophosphamide and total body irradiation as a conditioning regimen for bone marrow transplantation in rats (a preliminary report).
The longterm survival and occurrence of neoplastic and nonneoplastic lesions following total body irradiation (TBI), 8.5 Gy, with or without additional cyclophosphamide (Cy; 100 mg kg-1 i.p.) treatment as a conditioning regimen for bone marrow transplantation (BMT) were studied in male BN/BiRij rats. The two groups of rats that were treated with Cy (Cy and Cy + TBI) that survived beyond 100 days after treatment, had a severely decreased median (post treatment) survival time (Cy + TBI: 14.5 months and Cy: 14.1 months). Survival time in the TBI group was moderately decreased (18.5 months) as compared with the untreated controls (27.2 months). All treatment modalities were carcinogenic according to the raw data. After Cy-treatment a high incidence of, frequently multiple, malignant nerve-sheath tumours (Cy: 66 per cent, Cy + TBI: 31 per cent, controls: 2 per cent) was observed. TBI induced an increased occurrence of a great variety of tumours, especially mesenchymal tumours. This effect was more pronounced in animals receiving TBI alone as compared to animals receiving the combined treatment of Cy + TBI; an effect that most likely resulted from the longer median survival after TBI. The multi-target effect of TBI was also reflected in the occurrence of nonneoplastic effects in a variety of tissues, including high incidences of biliary cysts in the liver and severe testicular atrophy. The most important Cy-induced nonneoplastic lesion was incisor dysplasia, which resulted in feeding problems that could only be partly overcome by administering powdered food. Early mortality in the Cy-treated groups was associated with emaciation and generalized organ atrophy. A more definitive estimate of the late effects of supralethal chemoradiotherapy as part of a treatment of malignant disease has to await the results of various conditioning regimens for BMT in rats employing the acute BN myelocytic leukaemia (BNML) as a rat model for human acute myelocytic leukaemia (AML).
Zurcher
C
C
Varekamp
A E
AE
Solleveld
H A
HA
Durham
S K
SK
De Vries
A J
AJ
Hagenbeek
A
A
D000818:Animals; D016026:Bone Marrow Transplantation; D003043:Cocarcinogenesis; D003520:Cyclophosphamide / Q000009:adverse effects*; D007180:Incisor / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D003520:Cyclophosphamide