title: Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment.
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.
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA. jswenber@email.unc.edu
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
authors.forename: Kun
authors.initials: K
authors.lastname: Lu
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Moeller
authors.forename: Lina
authors.initials: L
authors.lastname: Gao
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Upton
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Starr
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D004247:DNA / Q000187:drug effects*; D018736:DNA Adducts / Q000737:chemistry / Q000633:toxicity*; D005027:Ethylene Oxide / Q000633:toxicity; D005557:Formaldehyde / Q000633:toxicity; D006801:Humans; D017720:Molecular Epidemiology / Q000379:methods*; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D018570:Risk Assessment; D014752:Vinyl Chloride / Q000633:toxicity
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D005557:Formaldehyde; D004247:DNA; D005027:Ethylene Oxide; D014752:Vinyl Chloride