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Breast Cancer Research and Treatment

, Volume 11, Issue 3, pp 231–240 | Cite as

Role of polyamines in the growth of hormone-responsive experimental breast cancerin vivo

  • Andrea Manni
  • Betty Badger
  • Gordon Luk
  • Carol Wright
  • Richard Caplan
  • Howard Rockette
  • Mary Bartholomew
  • S. Rafeeq Ahmed
Report

Summary

We have provided evidence for a critical role of polyamines in the growth of the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumorin vitro. The present experiments were designed to test whether polyamines are involved in the growth of this experimental tumorin vivo. To test this hypothesis, groups of rats bearing NMU-induced mammary cancers were randomly allocated to receive no treatment or escalating doses of the polyamine biosynthesis inhibitor α-difluoromethyl-ornithine (DFMO) (0.5%, 1%, 2%, 3% in drinking water). DFMO inhibited tumor growth in a dose-dependent fashion and consistently reduced tumor putrescine level. To evaluate the time dependency of this effect, additional groups of rats received either no treatment or 2% DFMO for 3, 7, 14, and 21 days. At all times DFMO suppressed tumor putrescine level as well as spermidine to spermine ratio. Finally, exogenous administration of putrescine (200 mg/kg/i.p./day × 21 days) given concomitantly with DFMO restored tumor growth, partially repleted tumor putrescine level, and raised the spermidine to spermine ratio to control levels. Putrescine, given alone, had no significant effect on either tumor polyamine levels or tumor growth. Except for modest weight loss, no major toxicity was encountered. These results indicate that polyamines play an important role in the growth of the NMU rat mammary tumorin vivo. The interaction between polyamines and hormones in supporting NMU mammary tumor growthin vivo remains to be elucidated.

Key words

polyamines NMU mammary tumor 

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Copyright information

© Kluwer Academic Publishers 1988

Authors and Affiliations

  • Andrea Manni
    • 1
  • Betty Badger
    • 1
  • Gordon Luk
    • 3
  • Carol Wright
    • 1
  • Richard Caplan
    • 4
  • Howard Rockette
    • 4
  • Mary Bartholomew
    • 2
  • S. Rafeeq Ahmed
    • 1
  1. 1.Department of MedicineThe Milton S. Hershey Medical Center, The Pennsylvania State UniversityHersheyUSA
  2. 2.Behavioral ScienceThe Milton S. Hershey Medical Center, The Pennsylvania State UniversityHersheyUSA
  3. 3.The Oncology Center and Department of MedicineThe Johns Hopkins University, School of MedicineBaltimoreUSA
  4. 4.Department of BiostatisticsUniversity of PittsburghPittsburghHersheyUSAUSA

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