Genotoxic evaluation and gene expression in Mus musculus exposed to landfill soil simulated leachates

Exposure to hazardous substances from landfill frequently occurs through complex chemical mixtures called leachates with a significant source of environmental and health concern. This study generated simulated leachates from soils collected at three landfill sites, Obajana (OBSL), Ajaokuta (AJSL), and Anyigba (AYSL) simulated leachate and evaluated their genotoxic and molecular effects using Mus musculus as a model organism. The leachates were characterized for physicochemical properties and leachate pollution indices. Mice orally exposed to 4 different (15 - 75 %) concentrations of each test leachates were examined for clinical signs of toxicity, body weight gain during exposure, genotoxicity and gene expression. Chemical analyses revealed elevated concentrations of biochemical oxygen demand (BOD), chemical oxygen demand (COD), total dissolved solid (TDS), and heavy metals. The clinical toxicity signs observed include skin brownish discoloration, hair loss, ungroomed hair, reduced food consumption and decreased activities, neck abscesses and measurable tumour development. All leachates produced significant concentration dependent increases in DNA damage relative to the negative control, as demonstrated by alterations in polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) ratios (PCE/NCE), increased frequencies of Micronucleated Polychromatic Erythrocyte (MNPCE) and Micronucleated Normochromatic Erythrocyte (MNNCE), and elevated olive tail moment, tail DNA (%), and tail length. Genotoxicity or DNA damage induction follow the order AJSL > OBSL > AYSL. The observed effects may reflect individual, synergistic, or antagonistic interactions among the chemical constituents of the leachates. RT-qPCR gene expression analysis revealed significant down regulation of HSP70 and TNF-α in liver tissue, indicating suppression of stress response and inflammatory pathways consistent with potential immunosuppression and impaired cellular defense. These findings demonstrate that leachates from landfill sites possess substantial genotoxic and immunomodulatory potential, underscoring the risk to exposed populations and the need for strengthened waste management and environmental monitoring.