Rapid progression of high-grade gliomas contributes to the poor survival rates of patients, particularly those with aggressive and heterogeneous brain tumors such as glioblastomas (GBMs). Before the onset of tumor symptoms, there exists a vulnerable period during which exposure to environmental factors could exacerbate glioma tumorigenicity. Alcohol (EtOH) is one such factor that has been shown to increase tumor size and vascularization of melanomas in xenograft mouse models and invasion of breast cancer cells in vitro. Currently, whether EtOH exposure promotes glioma progression in vivo is unknown. Here, we induced fluorescently labeled gliomas in immune-competent mice by injecting and electroporating Cre + CRISPR plasmids to delete tumor suppressor genes in neural progenitors lining the right lateral ventricle. Asymptomatic tumor mice were exposed to EtOH or Air vapors via inhalation chambers for five days, followed by two days of rest, then another five days of exposure. This paradigm produced blood ethanol concentrations (BECs) similar to episodic binge drinking, averaging ∼200 mg/dL on the final day of exposure. We found that EtOH exposure acutely increased tumor vascularization and invasion to the contralateral hemisphere. Notably, EtOH-exposed male mice exhibited a significant decrease in survival compared to Air-exposed controls and EtOH-exposed female mice. Overall, our study is the first to demonstrate that developing primary gliomas are susceptible to the tumorigenic effects of EtOH, with males being more vulnerable to increased mortality.
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