Potential human cancer risk posed by N-nitrosamines has been recognized for decades based on positive cancer studies in almost 40 animal species. Despite the widespread recognition of potential cancer risk from this class of chemicals, there is limited mechanistic insight into cellular responses and sequelae associated with nitrosamine exposure. A 2025 Symposium Session titled “N-Nitrosamines in Water and in Drugs: Occurrence, Detection, Biological Effects, and Regulation” highlighted research designed to investigate molecular and cellular responses to nitrosamine exposure.
Work from the Massachusetts Institute of Technology (MIT)’s Engelward Laboratory was presented that evidenced persistent changes in gene expression following nitrosamine exposure, with over 1,000 genes upregulated following exposure to N-nitrosodimethylamine (NDMA), even after repair of DNA adducts.
Lindsay Volk, PhD, of MIT presented her NIEHS-funded research designed to explore whether age influences the effects of NDMA exposure using a genetically modified mouse model deficient in DNA repair. Following drinking water exposure among juvenile and adult mice, Dr. Volk found comparable DNA adduct frequencies. The similarity in responses between these two groups disappeared, with severe genotoxicity and DNA damage seen in juvenile mice that was not seen in adult mice following NDMA exposure. Liver injury among young mice was associated with stimulated tissue regeneration as well as increased mutation frequencies compared to adult mice.
Despite recent government efforts to regulate nitrosamine impurities in pharmaceuticals, nitrosamine exposure from other sources is still on-going and poses a health risk to humans. Research presented during this Symposium Session demonstrates that studies in younger animals should be prioritized in order to ensure that cancer risks from this class of chemicals are not underestimated among those most vulnerable.
This blog reports on the Symposium Session titled “N-Nitrosamines in Water and in Drugs: Occurrence, Detection, Biological Effects, and Regulation” that was held during the 2025 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.
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