Quantitative genotoxicity assessment of N-nitrosodimethylamine in mice by error-corrected next-generation sequencing and DNA methylation quantification for toxicity threshold determination

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Greetings to the community!

I found this recent article - however no free access.

In the study, high-accuracy LC-MS/MS combined with error-corrected next-generation sequencing (ecNGS) to assess NDMA-induced DNA adduction and somatic mutations in mice using the quantitative benchmark dose (BMD) approach, aiming to improve the risk assessment of NDMA-contaminated pharmaceuticals and demonstrate the potential implementation of ecNGS in regulatory decision-making.

NDMA induced dose-dependent increases in both DNA adduction and somatic mutations in liver tissues, with significant increases in mutation frequencies observed at ≥ 1 mg/kg/day. NDMA induced mutations mainly with CG > TA and TA > CG transitions, exhibiting a signature resembling COSMIC signature 11, the mutational profile of alkylating agents. BMD50 (90% CI) was estimated as 0.08-0.32 mg/kg for N7-methylguanine and 1.64-3.83 mg/kg for mutations. Permitted daily exposure (PDE) for NDMA was calculated from the lower confidence limit of BMD50 (BMDL50) of genotoxic endpoints using appropriate uncertainty factors, revealing a PDE value of 245 ng/day for NDMA-induced mutation.

The link is : Quantitative genotoxicity assessment of N-nitrosodimethylamine in mice by error-corrected next-generation sequencing and DNA methylation quantification for toxicity threshold determination | Archives of Toxicology

If anyone can open and would like to share it, that would be wonderful and very helpful :slight_smile:

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Hi @elenipoliti

Clicking on the link seems to show the whole article for me.

(Several times I have purchased copies of articles, only for them to become available for free a couple of days later).

It may be worth trying again.

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Yes. you are right. thank you :slight_smile: