Estrogen metabolism and human papillomavirus-induced tumors of the larynx: chemo-prophylaxis with indole-3-carbinol.
A relationship was established between estradiol 16 alpha-hydroxylation, papillomavirus and its malignant sequelae. In this study, we determined that 16 alpha-hydroxylation was substantial in normal larynx and further increased in laryngeal papillomas. Estradiol or 16 alpha-hydroxyestrone stimulated proliferation in both kinds of cells while 2-hydroxyestrone was antiproliferative. Indole-3-carbinol, which induces 2-hydroxylation, abrogated the proliferative effects of estradiol. In immunocompromised mice, papilloma cysts formed in HPV-11 infected laryngeal tissue implanted under the renal capsules in 100% of control mice but only in 25% of mice fed indole-3-carbinol.
Department of Otolaryngology, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY 11042.
L
L
Newfield
A
A
Goldsmith
H L
HL
Bradlow
K
K
Auborn
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases; D002455:Cell Division / Q000187:drug effects; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000494:pharmacology; D006900:Hydroxylation / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use*; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control*; D007830:Larynx / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control*; D010212:Papilloma / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D027383:Papillomaviridae; D039181:Steroid 16-alpha-Hydroxylase; D014183:Transplantation, Heterologous; D014412:Tumor Virus Infections / Q000150:complications*
D016588:Anticarcinogenic Agents; D004965:Estrogen Antagonists; D004967:Estrogens; D006894:Hydroxyestrones; D007211:Indoles; C026702:16-hydroxyestrone; C016517:indole-3-carbinol; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D039181:Steroid 16-alpha-Hydroxylase