Marriage of a medium-term liver model to surrogate markers--a practical approach for risk and benefit assessment.
The need for a reliable medium-term alternative to traditional long-term rodent test protocols for carcinogen risk assessment is pressing given the immense variety of compounds being developed for introduction into the human environment. The established lack of a complete correlation between mutagenicity and carcinogenicity means that recourse must be made to an in vivo model. Optimally, this model should be able to detect not only complete carcinogenic or promoting potential but also any ability to inhibit neoplasia. In order to be effective, it must take into account the available detailed knowledge on mechanisms of action of carcinogens and modulating agents. The Ito model, for which a uniquely comprehensive set of background data has already been accumulated, has a solid scientific basis; this model utilizes quantitative data for glutathione S transferase-positive foci as the preneoplasia-based surrogate end point (PSE). A very practical candidate for routine 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.
Moore
M A
MA
Division of Chemotherapy, National Cancer Research Center, Tokyo, Japan.
Tsuda
H
H
Tamano
S
S
Hagiwara
A
A
Imaida
K
K
Shirai
T
T
Ito
N
N
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004195:Disease Models, Animal; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D018570:Risk Assessment
D015415:Biomarkers; D002273:Carcinogens; D005982:Glutathione Transferase