Molecular Dosimetry of Endogenous and Exogenous O⁶‑Methyl-dG and N7-Methyl‑G Adducts Following Low Dose [<i>D</i>₃]‑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 [<i>D</i>₃]-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