NAD + Acts as a Protective Factor in Cellular Stress Response to DNA Alkylating Agents.
Level 5 - mechanism / opinion, no new human data
In vitro cell culture experiment without human participants or animal models.
PubMed 37830610 · doi:10.3390/cells12192396
What was done
The authors investigated the role of NAD+ depletion and supplementation in cellular stress responses to sulfur mustard derivatives, specifically 2-chloroethyl-ethyl sulfide (CEES) and mechlorethamine (HN2). Human immortalized keratinocytes (HaCaT) and monocyte-like cells (THP-1) were treated with the NAD+ booster nicotinamide riboside (NR) or the NAD+ synthesis inhibitor FK866. Cellular NAD+ levels, poly(ADP-ribose) response, ATP levels, DNA damage repair, and short- and long-term cytotoxicity were evaluated.
What was found
The abstract reports no numerical values. In HaCaT cells, NR increased NAD+ levels and elevated poly(ADP-ribose) response, but did not alter ATP levels, DNA repair, or cytotoxicity from the mustard agents. Depleting NAD+ with FK866 sensitized HaCaT cells to genotoxic stress from CEES, an effect rescued by NR supplementation. In THP-1 cells, NR-induced elevation of NAD+ attenuated mustard compound toxicity, especially following CEES exposure.
Why it matters
This study demonstrates that NAD+ modulation exhibits cell-type-specific and compound-specific protective effects against alkylating agents, mitigating toxicity in monocytes but not directly preventing cytotoxicity in keratinocytes.
Limits
The study is restricted to in vitro experiments using two immortalized cell lines, limiting applicability to primary human tissues and whole-organism toxicity. The abstract provides no quantitative data, exposure concentrations, replicate numbers, or effect sizes.
Cited by
- supports Activation of PARP enzymes during DNA repair acts as a major consumer and drain on cellular NAD+ levels.