bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.06.15.659797

Acute exposure to groundwater contaminants mixture of nitrate, atrazine and imidacloprid impacts growth kinetics of poultry cecal microbiomes and significantly decreases Caco-2 cell viability

Majumder, E. L.- W.·Chatman, C. C.
View original source ↗Export metadata ↓

Abstract

Atmospheric deposition, and agricultural runoff or erosion events have substantially contributed to groundwater pollution throughout the USA. This can become troublesome in states like Wisconsin where 68% of the population rely on groundwater for their drinking water source. As such, exposome research must account for the complexity and frequency of environmental exposures. This study aimed to elucidate chemical-biological interactions and adverse outcome pathways associated with an environmentally relevant mixture of agricultural chemicals detected in Wisconsin groundwater via in vitro and in silico methodologies. Using in vitro models, we determined that a ternary mixture of environmentally relevant concentrations of nitrate, atrazine and imidacloprid resulted in an overt decline in growth rate to the poultry cecal microbiome compared to each chemical singularly. Further, there was a decrease in Caco-2 cell viability in various two-chemical combinations. In silico methods analyzed contaminants detected in Wisconsin groundwater wells from across the state and prioritized two groundwater wells as potential for health concerns. Prioritized chemicals in these groundwater wells were linked to nine gene targets and several adverse outcome pathways. In all, the results demonstrated that there is chemical-biological interaction between these model organisms agricultural and chemical mixtures at real world exposure concentrations. HighlightsO_LIin silico methods were able to predict potential adverse effects for communities utilizing these groundwater wells C_LIO_LI8 out of 9 chemicals prioritized with in silico tools were herbicides C_LIO_LIA ternary mixture of nitrate, imidacloprid and atrazine resulted in a decline in growth rate for poultry cecal microbiome C_LIO_LICaco-2 cells significantly impacted by two-chemical combinations but not ternary mixtures C_LI

Explore related subjects

pharmacology and toxicologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Majumder, E. L.- W., Chatman, C. C.. 2025-06-20. Acute exposure to groundwater contaminants mixture of nitrate, atrazine and imidacloprid impacts growth kinetics of poultry cecal microbiomes and significantly decreases Caco-2 cell viability. https://doi.org/10.1101/2025.06.15.659797

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Context and exposure history shape insecticide sensitivity in Drosophila melanogaster

Current insecticide toxicology still lacks an integrated understanding of how lethal and sublethal exposure shape organismal performance across biologically and environmentally relevant contexts. In particular, insecticide susceptibility may vary with physiological state, environmental conditions, and recent exposure history, factors that are only partially captured by standardized toxicity assessments. Here, using Drosophila melanogaster, we systematically compared responses to three insecticides with distinct modes of action - acetamiprid, chlorantraniliprole, and deltamethrin - across developmental stages, sexes, adult ages, and ambient temperatures. Insecticide sensitivity varied substantially across these conditions, with temperature modulating toxicity in a compound-dependent manner. Notably, deltamethrin caused substantial lethality at concentrations more than 10,000-fold below approved field application rates. Beyond these context-dependent differences in acute toxicity, sublethal pre-exposure to each insecticide rapidly reduced lethality during a subsequent challenge with the same compound, with increased tolerance already detectable after 24 h. Importantly, these exposure conditions that enhanced insecticide tolerance were associated with reduced resistance to environmental challenges, including heat and nutrient starvation, revealing a potential trade-off in organismal stress resilience. Acetamiprid exposure further altered reproductive performance in a concentration-dependent manner, with higher exposure reducing egg production while increasing developmental success among the resulting offspring, such that the number of offspring reaching adulthood remained largely unchanged. Together, these findings demonstrate that insecticide susceptibility is highly context dependent and can be rapidly modified by recent exposure history. We identify short-term, compound-specific, and potentially costly tolerance as an underappreciated consequence of insecticide exposure and highlight the importance of incorporating biological context, environmental conditions, and sublethal exposure history into pesticide risk assessment.

pharmacology and toxicology↗
bioRxiv2026

Aquaporin-9 and aquaporin-10 but not aquaporin-3 confer susceptibility to dimethylarsinic acid genotoxicity in human cells

Human metabolism converts inorganic arsenic to the pentavalent methylated species MMA(V) and DMA(V), the forms most people excrete, and the forms long read as the end of a detoxification pathway. Whether a transporter sets how much of these metabolites reaches the genome has not been tested in a mammalian cell. We expressed human AQP3, AQP7, AQP9 or AQP10 in HEK293T and MRC5-SV40 cells and measured gamma-H2AX by flow cytometry across dose series of As(V), MMA(V) and DMA(V), pairing every aquaporin with a GFP-Tubulin control and an untransfected mock acquired in the same replicate. As(V) was inactive in HEK293T cells and only weakly active in MRC5-SV40 cells to 20 micromolar, and both methylated species damaged DNA only in the millimolar range, DMA(V) being the more potent of the two in both cell lines. Against that weak baseline, AQP9 and AQP10 raised DMA(V)-induced gamma-H2AX in HEK293T cells by roughly 17 percentage points over the matched control, more than doubling the damage the same exposure produced in control cells, whereas AQP3 and AQP7 changed it not at all. AQP9 alone remained active with MMA(V). The ranking held in MRC5-SV40 fibroblasts at one-sixth the size, and within single wells the damage rose with the amount of AQP9 a cell carried while the control was flat. Aquaglyceroporins therefore discriminate among arsenic species, and AQP9 and AQP10 turn a weakly genotoxic metabolite into a substantially more genotoxic one.

pharmacology and toxicology↗
bioRxiv2026

Quantitative Systems Pharmacology Model for Trop-2 Targeting Antibody-Drug Conjugate in Triple-Negative Breast Cancer

TROP2-targeted antibody-drug conjugates (ADCs) have demonstrated promising clinical activity in triple-negative breast cancer (TNBC) as monotherapies; however, therapeutic benefit varies among patients. Combination strategies pairing TROP2-targeted ADCs with immune checkpoint inhibitors are also being investigated. Elucidating the mechanistic drivers of ADC monotherapy variability and enabling the rational development of combination regimens require computational frameworks that integrate ADC pharmacology with tumor-immune interactions. A quantitative systems pharmacology (QSP) model is presented that incorporates an ADC module into our established immuno-oncology model for TNBC. The module captures ADC and payload pharmacokinetics and pharmacodynamics. TNBC heterogeneity is represented by two tumor cell clones with high and low TROP2 expression, informed by prior characterizations, and differential sensitivity to the ADC payload is incorporated as an intrinsic property of each clone. Although generalizable, the model was applied to the TROP2-targeted ADC sacituzumab govitecan (SG, TRODELVY). A virtual patient cohort was generated using Latin hypercube sampling and calibrated against objective response rate (ORR) data from SG Phase I/II TNBC basket trial. The model predicted an ORR of 33.2% consistent with ASCENT study (NCT02574455). Simulations suggest TROP2-mediated delivery contributes modestly to SG efficacy with tumor exposure driven largely by systemically released SN-38 payload being sufficient to induce cytotoxicity. Tumor heterogeneity emerged as a key determinant of response with ORR increasing as the fraction of payload-sensitive clones increased. Overall, this QSP framework for TROP2-targeted ADCs accounts for TNBC heterogeneity and is extendable to other ADCs and targets enabling interrogation of ADC mechanisms of action in conjunction with tumor-immune interactions.

pharmacology and toxicology↗