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Review
. 2011 Mar;120 Suppl 1(Suppl 1):S130-45.
doi: 10.1093/toxsci/kfq371. Epub 2010 Dec 16.

Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment

James A Swenberg  1 , Kun Lu, Benjamin C Moeller, Lina Gao, Patricia B Upton, Jun Nakamura, Thomas B Starr
Affiliations
Review

Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment

James A Swenberg et al. Toxicol Sci. 2011 Mar.

Abstract

There is a strong need for science-based risk assessment that utilizes known data from diverse sources to arrive at accurate assessments of human health risk. Such assessments will protect the public health without mandating unreasonable regulation. This paper utilizes 30 years of research on three "known human carcinogens": formaldehyde, vinyl chloride (VC), and ethylene oxide (EO), each of which forms DNA adducts identical to endogenous DNA adducts in all individuals. It outlines quantitative data on endogenous adducts, mutagenicity, and relationships between endogenous and exogenous adducts. Formaldehyde has the richest data set, with quantitative data on endogenous and exogenous DNA adducts from the same samples. The review elaborates on how such data can be used to inform the current risk assessment on formaldehyde, including both the biological plausibility and accuracy of projected risks. Finally, it extends the thought process to VC, EO, and additional areas of potential research, pointing out needs, nuances, and potential paths forward to improved understanding that will lead to strong science-based risk assessment.

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Figures

FIG. 1.
FIG. 1.
Formation of hydroxymethyl DNA adducts induced by formaldehyde.
FIG. 2.
FIG. 2.
Molecular dosimetry of N2-hydroxymethyl-dG adducts in rats exposed to formaldehyde.
FIG. 3.
FIG. 3.
Formation of exogenous dG adducts in rats and monkeys exposed to 1.9 and 6.1 ppm formaldehyde (1-day exposure for rats and 2-day exposure for monkeys).
FIG. 4.
FIG. 4.
Metabolism of VC and formation of DNA adducts from CEO.
FIG. 5.
FIG. 5.
Metabolism of ethylene and formation of DNA adducts from EO.
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