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Creating context for the use of DNA adduct data in cancer risk assessment: I. Proposed framework for data organization *
Citation:
JARABEK, A. M., L. H. Pottenger, D. Casciano, M. Embry, J. Kim III, J. PRESTON, M. M. Vijayaraj, R. Schoeny, D. Shuker, J. Skare, J. A. SWENBERG, G. Williams, AND E. Zeiger. Creating context for the use of DNA adduct data in cancer risk assessment: I. Proposed framework for data organization *. CRITICAL REVIEWS IN TOXICOLOGY. CRC Press LLC, Boca Raton, FL, 39(8):659-678, (2009).
Impact/Purpose:
This manuscript is one of a set that has resulted from an ILSI HESI committee effort exploring how to use emerging DNA adduct data in risk assessment. It represents a consensus effort and evaluation ofthe state-of-the-science regarding interpretation of DNA adducts and an attempt to integrate them into the current exposure-dose-response conceptual construct used in regulatory risk assessment. The other manuscript was devoted to issues of evaluating the quality of DNA adduct measurement data.
Description:
The assessment of human cancer risk from chemical exposure requires the integration of diverse types of data. Such data involve effects at the cell and tissue levels. This report focuses on the specific utility of one type of data, namely DNA adducts. Emphasis is placed on the appreciation that such DNA adduct data cannot be used in isolation in the risk assessment process but must be used in an integrated fashion with other information. As emerging technologies provide even more sensitive quantitative measurements of DNA adducts, integration that establishes links between DNA adducts and accepted outcome measures becomes critical for risk assessment. The present report proposes an organizational approach for the assessment of DNA adduct data (e.g., type of adduct, frequency, persistence, type of repair process) in concert with other relevant data such as dosimetry, toxicity, mutagenicity, genotoxicity, and tumor incidence, to inform characterization ofthe mode-of-action. DNA adducts are considered biomarkers of exposure while gene mutations and chromosomal alterations are often biomarkers of early biological effect and also can be bioindicators of the carcinogenic process. Page
