Further characterization of the leukemogenic activity of haloperidol in mice.
Haloperidol, a butyrophenon, is widely used for the treatment of psychotic disorders in man. Recently we reported that this drug causes, with high incidence, the development of monocytic-myeloid leukemias in male NMRI mice upon 5 X 5 mg/kg i.p. administration. Here we present evidence for the leukemogenic effect of haloperidol in two other strains of mice (XVII AKF1 hybrids, and the low leukemic BALB/c/BOM). The strain-dependent incidence of leukemias ranged both in males and females between 34% (AKR) and 69% (XVII AKF1) with average latencies between approximately 200 (AKR) and 600 (BALB/c) days. On the basis of cytological and cytochemical criteria the predominating type of leukemias was classified as monocytic-myeloid. These leukemic were serially transplantable. Cell-free extracts of leukemic tissues did not induce the disease indicating that no virus was activated by haloperidol. However, when the drug was administered to AKR mice after a suboptimal dose of nitrosomethylurea (NMU), a higher incidence of mixed-type leukemias was observed as with haloperidol alone. NMU alone induced lymphatic leukemias with proven viral involvement. The tumor promoter 12-0-tetradecanoylphorbol-13-acetate did not influence haloperidol-induced leukemogenesis.
Wunderlich
V
V
Academy of Sciences of the German Democratic Republic, Central Institute of Cancer Research, Berlin.
Fey
F
F
Sydow
G
G
D000818:Animals; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000633:toxicity*; D007942:Leukemia, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D008770:Methylnitrosourea; D006220:Haloperidol; D013755:Tetradecanoylphorbol Acetate