Papers of the Month
Extramural
By Janelle Weaver
Arsenic may promote ovarian cancer through DNA damage, inflammation
Arsenic may contribute to ovarian cancer through the interplay between DNA damage and inflammatory signaling pathways, according to researchers supported in part by NIEHS.
Arsenic is a toxic element commonly found in groundwater and certain foods, representing a major public health concern. Long-term exposure has been linked to several types of cancer, including ovarian cancer. However, the precise mechanisms underlying this link have remained unclear.
In this study, the researchers examined the cellular and molecular effects of chronic arsenic exposure using human cultures derived from the ovarian surface and fallopian tube. They found that prolonged exposure to arsenic was toxic to the cells, leading to the formation of abnormally large cells with multiple nuclei. Some of these damaged cells appeared to engulf debris from neighboring cells that had died from chronic toxic stress. In addition, the arsenic-exposed cells showed signs of DNA damage, nuclear abnormalities, markers of cancer stem cells, and activation of the NF-κB pathway, a key driver of inflammation through molecules called cytokines.
Taken together, the results suggest that arsenic exposure may promote cancer growth by triggering inflammation and genomic instability. According to the authors, this research could help improve early detection and treatment of ovarian cancer.
Citation: Andrade-Feraud CM, Acanda de la Rocha AM, Berlow NE, Duque S, Velazco A, Castillo D, Holcomb B, Coats ER, Ghurani YR, Lucey CM, Pearson B, Guilarte TR, Azzam DJ. 2025. Chronic arsenic exposure of ovarian surface and fallopian tube cultures induces giant and/or multinucleated cells with phagocytosis-like properties and an inflammatory phenotype. Toxicol Appl Pharmacol 500:117394.
Inhaled iron may contribute to aging-related brain disorders
Whole body inhalation of iron, a common contaminant of air pollution, produces signs of neurodegenerative diseases in mice, and the specific effects vary by sex, according to an NIEHS-supported study.
Both increased levels of iron in the brain and air pollution exposure have been linked to various neurodegenerative disorders. Iron is particularly elevated in subway systems, and nanosized iron particles can travel directly from the nose into the olfactory bulb region of the brain. The researchers investigated whether inhaled iron from air pollution may contribute to neurodegenerative disorders.
Toward that goal, they exposed mice to iron oxide nanoparticles in the air at levels similar to those found in subway systems. Tissue samples from the olfactory bulb confirmed that inhaled iron oxides were present in the brain. Female mice exposed to iron developed features of Alzheimer’s disease, including memory impairments and increased levels of tau proteins in hippocampus, a brain region important for memory. In contrast, male mice showed enlargement of the substantia nigra pars compacta, a brain region linked to movement impairments seen in Parkinson’s disease.
According to the authors, long-term exposure to inhaled iron from air pollution may contribute to the buildup of iron in the brain over time, potentially raising the risk of neurodegenerative diseases as people age.
Citation: George JV, Hornburg KJ, Merrill A, Marvin E, Conrad K, Welle K, Gelein R, Chalupa D, Graham U, Oberdörster G, Johnson GA, Cory-Slechta DA, Sobolewski M. 2025. Brain iron accumulation in neurodegenerative disorders: does air pollution play a role? Part Fibre Toxicol 22(1):9.
Puberty shapes the adolescent gut microbiome
The gut microbiome of adolescents may be influenced by hormones, puberty, and sociodemographic characteristics, according to an NIEHS-supported study.
Microbes residing in the gut play a key role in health. However, relatively few studies have been conducted on the adolescent microbiome, which may respond to hormonal changes during puberty. Moreover, it has not been clear how early life factors may influence the microbiome over the lifetime.
To shed light on this topic, the researchers analyzed the fecal microbiome of 167 adolescents using advanced sequencing and machine-learning approaches. They found that Firmicutes was the most common group of bacteria in the adolescent gut. The study also showed that sociodemographic factors such as household income and race or ethnicity were consistently linked to bacterial diversity and composition. For example, teens from higher income households tended to have less diverse gut bacteria, with more Firmicutes and fewer bacteria from a group called Actinobacteria.
The researchers also observed differences in bacterial diversity and composition linked to sexual maturation and hormone concentrations. According to the authors, the findings suggest that the unique adolescent microbiome may be shaped by both early life and ongoing experiences – and that it could play an important role in long-term health. They recommend further research to better understand these connections.
Citation: Laue HE, Willis AD, Wang F, MacDougall MC, Xu Y, Karagas MR, Madan JC, Fleisch AF, Lanphear BP, Cecil KM, Yolton K, Chen A, Buckley JP, Braun JM. 2025. Early-life and concurrent predictors of the healthy adolescent microbiome in a cohort study. Genome Med 17(1):50.
Traffic air pollution may raise diabetes risk in children
Children who are exposed to traffic-related air pollution for long periods may be more likely to develop insulin resistance — a precursor to type 2 diabetes — by the time they reach adulthood. This may be partly due to accelerated growth rates during childhood, according to NIEHS-supported research.
Exposure to traffic-related air pollutants has been linked to type 2 diabetes. Individuals who have this chronic condition do not make or use insulin effectively, leading to persistently elevated levels of blood sugar, or glucose. Exposure to air pollution can also affect glucose metabolism among children, but the underlying mechanisms have not been clear.
The researchers gathered data from 282 participants from before birth to 24 years of age. They found that children exposed to traffic-related nitrogen oxides were more likely to have a higher body mass index (BMI) during adolescence and into adulthood. These changes in BMI explained approximately one-half of the impact of air pollution exposure on insulin resistance in young adults. According to the authors, the study emphasizes the potential value of implementing weight management strategies for children living in heavily polluted regions.
Citation: Guo F, Chen X, Howland S, Niu Z, Zhang L, Gauderman WJ, McConnell R, Pavlovic N, Lurmann F, Bastain TM, Habre R, Breton CV, Farzan SF. 2025. Childhood exposure to air pollution, body mass index trajectories, and insulin resistance among young adults. JAMA Netw Open 8(4):e256431.
(Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)