Papers of the Month
Extramural
By Julie Leibach
Increased wildfire activity could contribute to more infectious marine bacteria
Exposure to ash from wildfires that occur where nature meets development may enhance the growth of more infectious marine bacteria, NIEHS-funded researchers reported. Their findings provide insight into how extreme weather associated with climate change may contribute to disease spread.
Climate change is fueling wildfires that are encroaching into urban areas, producing ash containing metals that could eventually infiltrate aquatic ecosystems. However, little research exists on how wildfire ash might affect the growth and toxicity of Vibrio vulnificus, a bacterium responsible for most seafood-related deaths in the U.S.
The researchers collected ash from a burned vegetated area and a burned residential structure. Next, they treated batches of V. vulnificus with increasing concentrations of either vegetation ash, characterized by its iron levels, or structural ash, containing chromium, copper, and arsenic. In a separate experiment, they exposed the microorganisms to structural ash or vegetation ash for 24 hours and analyzed gene expression, or activity.
For vegetation and structural ash, higher metal content corresponded to slower V. vulnificus growth rates, suggesting that certain compositions of wildfire ash are toxic to the bacteria. However, V. vulnificus growth initially spiked after several hours of exposure to vegetation ash with low iron levels, indicating the bacteria could proliferate under the right conditions. Additionally, both types of ash increased expression of genes related to antibiotic and metal resistance, with more prominent effects tied to structural ash exposure.
The findings suggest that ash from fires occurring where wildlands mingle with buildings could contribute to the spread of more infectious strains of V. vulnificus, according to the authors. A better understanding of the effects of mixed ash on bacterial adaptation could inform models for predicting potential V. vulnificus outbreaks, they added.
Citation: Correa Velez KE, Alam M, Baalousha MA, Norman RS. 2024. Wildfire ashes from the wildland-urban interface alter Vibrio vulnificus growth and gene expression. Environ Sci Technol 58(19):8169-8181.
Health intervention shows reduced arsenic exposures among tribes
Exposure to arsenic from private wells declined among American Indian communities that received free kitchen faucet filters and periodic health check-ins through phone calls and home visits, according to NIEHS-funded researchers. Participants also reported greater use of filtered water for cooking and drinking, and an increased understanding of vulnerability to arsenic in drinking water.
Studies have found connections between chronic arsenic exposure and health problems, such as cardiovascular disease, diabetes, and some cancers among American Indians, who often live in rural communities that rely on private wells. However, little research has focused on developing and evaluating effective interventions to reduce those exposures among private well users.
The team recruited participants from a Northern Great Plains American Indian Nation whose private wells contained high arsenic levels. After receiving community input on study design and implementation, the researchers randomly divided 50 households into two groups. Both received free filter installation at the kitchen faucet, as well as three check-in phone calls from a mobile health program. One group also received three home visits from a local health promoter.
The team measured urinary arsenic levels in participants before filter installation and during a two-year follow-up period. By the end of the study, urinary arsenic levels had decreased by 47% across groups, with no significant difference between interventions. Self-reported exclusive use of filtered water for cooking and drinking tripled over that time.
The results show that point-of-use filter installation, combined with mobile health check-ins, can reduce arsenic exposure among American Indian communities, according to the authors. Given that public health interventions involving in-person visits can be costly and difficult to implement in rural areas, the findings could inform feasible arsenic mitigation programs among other private well users.
Citation: George CM, Zacher T, Endres K, Richards F, Bear Robe L, Harvey D, Best LG, Red Cloud R, Black Bear A, Skinner L, Cuny C, Rule A, Schwab KJ, Gittelsohn J, Glabonjat RA, Schilling K, O'Leary M, Thomas ED, Umans J, Zhu J, Moulton LH, Navas-Acien A. 2024. Effect of an arsenic mitigation program on arsenic exposure in American Indian communities: a cluster randomized controlled trial of the community-led Strong Heart Water Study program. Environ Health Perspect 132(3):37007.
New cell-based approach identifies genetic sensitivity to toxic exposures
NIEHS-funded researchers developed a new cell-based approach for studying how environmental contaminants, like arsenic, interact with our genes to affect health. The results could help identify molecular pathways underlying genetic sensitivity and resistance to environmental toxicants.
Arsenic is a widespread groundwater contaminant that can damage DNA and cells through a process called oxidative stress. However, the likelihood and severity of health outcomes associated with exposure depend on a person’s genetic makeup. Because studying genetic susceptibility in humans is difficult, research with genetically diverse rodent cells can shed light on gene-environment interactions.
The researchers used a minimally invasive method to collect mouse cells representing 226 genetically distinct lines. Next, they exposed the cells to a metabolic byproduct of arsenic at eight increasing concentrations for 24 hours. After exposure, the team stained the cells with fluorescent dyes so they could easily track morphological changes, which signified sensitivity to the exposure. Using a genetic mapping technique, they linked genetic variation in the cell lines to variation in the morphological responses to arsenic.
In parallel, the team evaluated gene expression in the cells and examined previously published findings to identify variation in genes and molecular pathways that regulate sensitivity to arsenic. Those variations related to arsenic transport, oxidative stress, and DNA damage. Although some of the identified genes had known ties to arsenic exposure, other genes — such as Xrcc2, involved in DNA damage repair — were new associations.
The findings provide a novel approach for studying interactions between environmental exposures and genes within a genetically diverse population, according to the authors. The technique could minimize the reliance on animal testing in chemical risk assessments, they added.
Citation: O’Connor C, Keele GR, Martin W, Stodola T, Gatti D, Hoffman BR, Korstanje R, Churchill GA, Reinholdt LG. 2024. Unraveling the genetics of arsenic toxicity with cellular morphology QTL. PLoS Genet 20(4):e1011248.
Cancer-preventive mechanisms of omega-3 fatty acids uncovered
Researchers funded by NIEHS identified mechanisms through which omega-3 fatty acids (omega-3s) may protect against lung cancer caused by exposure to polycyclic aromatic hydrocarbons (PAHs) in mice. The findings could inform lung cancer prevention strategies.
Extensive research has shown that lung cancer stems from exposure to cancer-causing chemicals in the environment, including PAHs found in air pollution and cigarette smoke. Studies suggest that omega-3s have anticancer effects, partially by inhibiting certain proteins called cytochrome P450 enzymes (CYP). Those proteins can convert PAHs to harmful derivatives that can damage DNA, potentially resulting in genetic mutations, or changes, that cause cancer. However, the mechanisms of omega-3 protection are not well understood.
Building on earlier work, the researchers explored how omega-3s might prevent cancer in mice exposed to PAHs. First, they fed omega-3 diets to regular mice and to groups of mice missing one of three CYP genes, then exposed them to PAHs. Next, the team used regular mice to examine how omega-3s might stop DNA damage. Finally, they investigated whether omega-3s interact with other cancer-related genes.
Following PAH exposure, levels of DNA damage declined in all mice fed omega-3s, including in those missing the cytochrome gene Cyp1b1. In mice with intact CYP genes, molecular analysis showed that omega-3s inhibited expression of CYP1B1, which reportedly plays a key role in converting PAHs to DNA-damaging derivatives, according to the authors. Additional experiments showed that omega-3s increased expression of a tumor-suppressing gene called RUNX3.
Taken together, the results suggest that omega-3s inhibit DNA damage via a CYP pathway and also promote tumor suppression. Future studies should explore the possibility of incorporating supplemental omega-3s into cancer prevention efforts, according to the authors.
Citation: Xia G, Zhou G, Jiang W, Chu C, Wang L, Moorthy B. 2024. Attenuation of polycyclic aromatic hydrocarbon (PAH)-induced carcinogenesis and tumorigenesis by omega-3 fatty acids in mice in vivo. Int J Mol Sci 25(7):3781.
(Julie Leibach is a senior science writer at MDB, Inc., a contractor for the NIEHS Division of Extramural Research and Training.)
