Aromatase inhibitors prevent spontaneous granular cell tumors in the distal female reproductive tract of Sprague-Dawley rats.
We recently established diagnostic criteria for granular cell changes in the distal female reproductive tract of rats. In a review of control animals from 9 carcinogenicity studies, we found that approximately 23% of animals had granular cell alterations. Because estrogen may play a role in the pathogenesis of granular cell alterations, we reviewed tissue sections from carcinogenicity studies with 2 aromatase inhibitors and found compound-related decreases in the incidence of granular cell changes. Since these aromatase inhibitors selectively prevent the conversion of androgenic steroids to the corresponding estrogens, these data further suggest that estrogen may play a role in the pathogenesis of granular cell tumors of the reproductive tract of rats.
Markovits
J E
JE
Novartis Pharmaceuticals, East Hanover, New Jersey 07936, USA. judit.markovits@pharma.novartis.com
Sahota
P S
PS
D000818:Animals; D047072:Aromatase Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017316:Fadrozole / Q000494:pharmacology*; D005260:Female; D016586:Granular Cell Tumor / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D014625:Vaginal Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; D017316:Fadrozole