Further characterization of the leukemogenic activity of haloperidol in mice.

Abstract

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.

• Authors: V Wunderlich, F Fey, G Sydow
• Journal: Neoplasma (Neoplasma) Vol. 34 Issue 4 Pg. 389-96 ( 1987) ISSN: 0028-2685 [Print] Slovakia
• PMID: 3658046 (Publication Type: Journal Article)

Chemical References

• Methylnitrosourea
• Haloperidol
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Drug Interactions
• Female
• Haloperidol (toxicity)
• Leukemia, Experimental (chemically induced, pathology)
• Male
• Methylnitrosourea (toxicity)
• Mice
• Mice, Inbred AKR
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Species Specificity
• Tetradecanoylphorbol Acetate (toxicity)