Creating context for the use of DNA adduct data in cancer risk assessment: I. Data organization.
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 of the mode of action. DNA adducts are considered biomarkers of exposure, whereas gene mutations and chromosomal alterations are often biomarkers of early biological effects and also can be bioindicators of the carcinogenic process.
Jarabek
Annie M
AM
National Health and Environmental Effects Research Laboratory, on detail from National Center for Environmental Assessment, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Pottenger
Lynn H
LH
Andrews
Larry S
LS
Casciano
Daniel
D
Embry
Michelle R
MR
Kim
James H
JH
Preston
R Julian
RJ
Reddy
M Vijayaraj
MV
Schoeny
Rita
R
Shuker
David
D
Skare
Julie
J
Swenberg
James
J
Williams
Gary M
GM
Zeiger
Errol
E
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts / Q000032:analysis*; D003625:Data Collection / Q000379:methods*; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis / Q000706:statistics & numerical data; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods
D002273:Carcinogens; D018736:DNA Adducts