Molecular Dosimetry of Endogenous
and Exogenous O<sup>6</sup>‑Methyl-dG and N7-Methyl‑G
Adducts Following
Low Dose [<i>D</i><sub>3</sub>]‑Methylnitrosourea
Exposures in Cultured Human Cells
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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<sup>6</sup>-methyl-dG
adducts in human lymphoblastoid cells exposed to low dose [<i>D</i><sub>3</sub>]-methylnitrosourea. Endogenous amounts of
both adducts remained nearly constant, while the exogenous adducts
showed linear dose-responses. The data show that O<sup>6</sup>-methyl-dG
adducts ≥1.8/10<sup>8</sup> 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