Joachim G. Liehr
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas
Estrogens are risk factors for human breast cancer and induce kidney tumors in Syrian hamsters. Mechanistic features of the estrogen-induced hamster kidney tumor model have been compared with corresponding aspects of human breast cancer to gain insight into the mechanism of human mammary oncogenesis. Shared characteristics point to a mechanism of metabolic activation of steroidal estrogens to 4-hydroxylated catechol metabolites that may undergo metabolic redox cycling, a mechanism of generation of reactive free radicals. Tumors may arise in cells genetically altered by various types of estrogen-induced DNA damage. At the same time, these altered cells may respond to estrogen receptor-mediated stimuli in support of cell transformation and growth. -- Environ Health Perspect 105(Suppl 3):565-569 (1997)
Key words: estradiol, breast cancer, estrogen-induced cancer, hamster kidney
This paper was presented in part at the Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer held 28-29 September 1995 in New Orleans, Louisiana. Manuscript received at EHP 6 June 1996; manuscript accepted 17 October 1996.
The skillful assistance of K. Obeck in the preparation of the manuscript is greatly appreciated.
Supported by grant 2551.95 from the John Sealy Memorial Foundation. The author is a National Institute of Environmental Health Sciences Center investigator (5P30ES06676).
Address correspondence to Dr. J.G. Liehr, Department of Pharmacology and Toxicology, University of Texas Medical Branch, 11th and Market Streets, Galveston, TX 77555-1031. Telephone: (409) 772-9624. Fax: (409) 772-9642. E-mail: liehr@marlin.utmb.edu
Abbreviations used: E2, 17ß-estradiol; LHP, lipid hydroperoxides; 2-OH-E2, 2-hydroxyestradiol; 4-OH-E2, 4-hydroxyestradiol.
Last Update: April 10, 1997