Journal Article

Comparative activity of <i>N</i>-(4-hydroxyphenyl)-all-<i>trans</i>-retinamide and α-difluoromethylornithine as inhibitors of lymphoma induction in PIM transgenic mice

David L. MCCormick, William D. Johnson, K.V.N. Rao, Teresa Bowman-Gram, Vernon E. Steele, Ronald A. Lubet and Gary J. Kelloff

in Carcinogenesis

Volume 17, issue 11, pages 2513-2517
Published in print November 1996 | ISSN: 0143-3334
Published online November 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.11.2513
Comparative activity of
                        N-(4-hydroxyphenyl)-all-trans-retinamide
                    and α-difluoromethylornithine as inhibitors of lymphoma induction in PIM
                    transgenic mice

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The activities of the retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR) and the polyamine synthesis inhibitor, α-difluoromethylornithine (DFMO), as inhibitors of lymphoma induction in PIM transgenic mice were evaluated. Lymphoma was induced in male PIM mice by a single intraperitoneal injection of 50 mg N-ethyl-N-nitrosourea (ENU) per kg body weight. Continuous dietary administration of 4-HPR (391, 196 or 98 mg/kg diet) or DFMO (1000, 500 or 250 mg/kg diet) was initiated immediately after ENU administration, and was continued until the end of the study at 35 weeks. At 20 weeks post-ENU, the high dose of 4-HPR reduced both lymphoma incidence and associated mortality. However, the protection conferred by 4-HPR represented a delay rather than an inhibition of neoplastic development, since both lymphoma incidence and mortality at study termination were similar in dietary controls and all groups treated with 4-HPR. DFMO had no effect on lymphoma incidence, latency or mortality at any point in the study. These results suggest that 4-HPR or other retinoids may be effective in the prevention of lymphoma induction, whereas inhibition of polyamine biosynthesis does not appear to present a useful mechanistic target for the chemoprevention of lymphoid neoplasia. The PIM transgenic mouse provides a useful in vivo model for the rapid evaluation of chemopreventive agents.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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