• Report

Sliced testis assay prevalidation: Multichemical study

Citation

Sloan, C., Tyl, R., George, J., & Goodman, A. (2004). Sliced testis assay prevalidation: Multichemical study. (Draft Final Report. WA 3-10, Task 8. RTI No. 65U-08055.003.029. Sponsor: Battelle Memorial Institute, Columbus, OH). Unknown Publisher.

Abstract

This study was designed to evaluate the sliced testis assay for the ability to screen chemicals with known mechanisms of action for anti-steroidogenic activity and/or for cytotoxicity. The 9 chemicals tested were aminoglutethimide (AG; positive control), 2,4-dinitrophenol (2,4-DNP; cytotoxicity control), flutamide, ketoconazole, vinclozolin, atrazine, dimethoate, finasteride, spironolactone, verapamil, and prochloraz. These chemicals, evaluated for anti-androgenic and/or cytotoxic effects in the in vitro sliced testis assay, produced the following results: Finasteride, a 5"-reductase inhibitor, prevents 5"-reductase from converting testosterone to dihydrotestosterone (DHT) in the testis and locally. DHT plays a major role in the perinatal determination of external male genitalia and structures of the lower male reproductive tract. In this assay, finasteride caused concentration-related decreases in testosterone levels; an opposite response of what was expected. Lactate dehydrogenase (LDH) levels were increased at 1000 :M finasteride, with no effects at 10 or 100 :M.