Marriage of a medium-term liver model to surrogate markers - A practical approach for risk and benefit assessment

Citation
Ma. Moore et al., Marriage of a medium-term liver model to surrogate markers - A practical approach for risk and benefit assessment, TOX PATHOL, 27(2), 1999, pp. 237-242
Citations number
37
Language
INGLESE
art.tipo
Editorial Material
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGIC PATHOLOGY
ISSN journal
0192-6233 → ACNP
Volume
27
Issue
2
Year of publication
1999
Pages
237 - 242
Database
ISI
SICI code
0192-6233(199903/04)27:2<237:MOAMLM>2.0.ZU;2-V
Abstract
The need for a reliable medium-term alternative to traditional long-term ro dent test protocols for carcinogen risk assessment is pressing given the im mense variety of compounds being developed for introduction into the human environment. The established lack of a complete correlation between mutagen icity and carcinogenicity means that recourse must be made to an in vivo mo del. Optimally, this model should be able to detect not only complete carci nogenic or promoting potential but also any ability to inhibit neoplasia. I n order to be effective, it must take into account the available detailed k nowledge on mechanisms of action of carcinogens and modulating agents. The Ito model, for which a uniquely comprehensive set of background data has al ready been accumulated, has a solid scientific basis; this model utilizes q uantitative data for glutathione S transferase-positive foci as the preneop lasia-based surrogate end point (PSE). A very practical candidate for routi ne application, its predictive power, its flexibility, and its capacity to incorporate a range of mechanism-based surrogate end points (MSEs) provide a powerful tool for attainment of the twin goals of detecting carcinogenic agents and identifying promising chemopreventors.