Modification of regression of virally xenogenized tumor cells by cyclophosphamide and busulfan.
Rat fibrosarcoma cells infected with Friend leukemia virus (FV-KMT-17) grow for a short time and then regress spontaneously in syngeneic hosts. This regression mechanism was examined by analyzing the immunomodulating action of the antitumor drugs busulfan (BU) and cyclophosphamide (CY). In preliminary experiments, the optimum dosages of BU and CY for the enhancement of DTH responses to SRBC were 10 mg/kg and 40 mg/kg respectively. Treatment of rats with BU (10 mg/kg) on day 5 induced the regression of KMT-17 cells, while in contrast, the same drug delayed the spontaneous regression of FV-KMT-17 cells. Pretreatment with CY (40 mg/kg) on day 5 did not affect the growth of KMT-17 or FV-KMT-17 cells. After the same treatment schedule, BU inhibited humoral antibody formation against SRBC and against virus-associated antigen (VAA), NK cell activity, and ADCC effector cell activity. On the other hand, CY did not affect the activities of NK cells or ADCC effector cells, although it significantly augmented the DTH responses to SRBC and the production of antibody to VAA but had no effect on production of antibodies to SRBC. These results suggest that NK cells and ADCC may play an important role in the initial stage of the spontaneous regression of FV-KMT-17 cells.
Morikawa
K
K
Laboratory of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Hamada
J
J
Itaya
T
T
Ishikawa
M
M
Takeichi
N
N
Hosokawa
M
M
Kobayashi
H
H
D000818:Animals; D002066:Busulfan / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D005622:Friend murine leukemia virus / Q000502:physiology*; D006084:Graft Rejection / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D009365:Neoplasm Regression, Spontaneous; D009368:Neoplasm Transplantation; D051381:Rats
D003520:Cyclophosphamide; D002066:Busulfan