title: Molecular dosimetry of endogenous and exogenous O(6)-methyl-dG and N7-methyl-G adducts following low dose [D3]-methylnitrosourea exposures in cultured human cells.
abstract: For DNA-reactive chemicals, a low dose linear assessment of cancer risk is the science policy default. In the present study, we quantitated the endogenous and exogenous N7-methyl-G and O(6)-methyl-dG adducts in human lymphoblastoid cells exposed to low dose [D3]-methylnitrosourea. Endogenous amounts of both adducts remained nearly constant, while the exogenous adducts showed linear dose-responses. The data show that O(6)-methyl-dG adducts ≥1.8/10(8) dG correlated with published studies that demonstrated significant increases of mutations under these conditions. The combined results do not support linear extrapolations to zero when data are available for science-based regulations.
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina , Campus Box 7431, Chapel Hill, North Carolina 27599-7431, United States.
authors.forename: Vyom
authors.initials: V
authors.lastname: Sharma
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Collins
authors.forename: Jean M
authors.initials: JM
authors.lastname: Clement
authors.forename: Zhenfa
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
mesh_terms: D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D006147:Guanine; C008450:7-methylguanine; D008770:Methylnitrosourea; C015558:O(6)-methyl-2'-deoxyguanosine; D003849:Deoxyguanosine