Molecular dosimetry of endogenous and exogenous O6-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 O6-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 O6-methyl- dG adducts ≥1.8/108 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. © 2014 American Chemical Society.