Cadmium Exposure May Induce Potential Brain Tumour Initiation by Regulating SHH, GLI1, BMI1 and P53 in the SHH-GLI1
Swalih P Ahmed1, Intezar Ali1, Mehdi H Shahi1
1Interdisciplinary Brain Research Centre (IBRC), JN Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
Background:
Cadmium, a toxic heavy metal, poses a significant risk to human health. Its potential to contribute to brain tumorigenesis is a growing concern. Brain tumours are notoriously difficult to treat due to their aggressive nature, poor prognosis and resistance to conventional therapies.
Purpose:
To investigate the impact of cadmium exposure on brain tumour development, focusing on its influence on the Sonic Hedgehog (SHH)-glioma-associated oncogene 1 (GLI1) signalling pathway and the stem cell marker B cell-specific Moloney murine leukaemia virus integration site 1 (BMI1).
Methods:
A total of 25 Wistar rats of 200-250 g body weight range were classified into five groups: Test groups one and two were orally administered with cadmium chloride in drinking water (30 mg/L, 60 mg/L). Positive controls one and two were administered orally with zinc in drinking water (30 mg/L and 60 mg/L) and the negative control group rats received double-distilled water continuously for 28 days. We calculated the rat's water intake each week. From the third to the fourth week, we observed behavioural changes using an open field test (OFT). The animals were sacrificed on day 29. Thereafter, the brain and hindbrain were separated for further assessment, including real-time reverse transcription polymerase chain reaction (RT-PCR) to measure gene expression levels of key genes in the SHH-GLI1 signalling pathway and stem cell markers.
Results:
Water intake decreased in both the test and the positive control groups. The OFT analysis revealed significant behavioural changes in all parameters of both the test and positive control groups compared to the negative control group, including movement patterns, speed, travel distance, activity levels and freezing behaviour. Gene expression indicates increased SHH, GLI1, BMI1 and tumour protein 53 (TP53) expression in both the test and positive control groups.
Conclusion:
Cadmium exposure may initiate and promote brain tumour development by regulating SHH, GLI1, BMI1 and TP53. This may disrupt the normal regulatory mechanisms of the SHH-GLI1 pathway.
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