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| 9: Mutat Res 1998 Jun 18;402(1-2):165-72 |
Kensler TW, Groopman JD, Roebuck BD.
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and
Public Health, Baltimore, MD 21205, USA. tkensler@jhsph.edu
Clinical cancer prevention studies that use disease as an endpoint are of
necessity, large, lengthy, and extremely costly. Development of the field of
cancer chemoprevention is being accelerated by the application of intermediate
markers to preclinical and clinical studies. Sensitive and specific analytic
methods have been developed for detecting and quantifying levels of covalent
adducts of aflatoxins with cellular DNA and blood proteins at ambient levels of
exposure. Such biomarkers can be applied to the preselection of exposed
individuals for study cohorts, thereby reducing study size requirements. Levels
of these aflatoxin-DNA and albumin adducts can be modulated by chemopreventive
agents such as oltipraz and chlorophyllin in experimental models. Overall, a
good concordance is seen between diminution of biomarkers and reductions in
tumor incidence and/or multiplicity in these settings. Thus, these markers can
also be used to rapidly assess the efficacy of preventive interventions.
However, the successful application of these biomarkers to clinical prevention
trials will be dependent upon prior determination of the associative or causal
role of the marker to the carcinogenic process, establishment of the
relationship between dose and response, and appreciation of the kinetics of
adduct formation and removal. The general approach that has been utilized for
the development, validation and application of aflatoxin-DNA and protein adduct
biomarkers to cancer chemoprevention trials is summarized. Copyright 1998
Elsevier Science B.V. All rights reserved.
Publication Types:
PMID: 9675269
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