Unraveling gene expression and genetic instability in dental fluorosis: Investigating the impact of chronic fluoride exposure

Abstract

Chronic fluoride exposure, even in small quantities, when continuously ingested by the human population, can lead to a significant public health concern known as fluorosis. Our understanding of the effects of fluoride on human health, as well as its potential to impact DNA, is limited. The present study aimed to assess genetic instability in 20 individuals diagnosed with dental fluorosis and 20 individuals without the condition from the state of Rio Grande do Sul, Brazil. The participants' dental fluorosis was evaluated using the Thylstrup-Fejerskov index (TF). To further evaluate genetic instability, several assays were conducted, including the alkaline and modified (+FPG) comet assay (using a visual score, VS), the buccal micronucleus (MN) cytome (BMCyt) assay, the cytokinesis-block MN (CBMN-Cyt) assay, and the measurement of telomere length (TL). In addition, the study utilized tools from Systems Biology to gain insights into the effects of fluoride exposure on humans, which aided in the selection and evaluation of mRNA expression levels of specific genes, namely PPA1 (inorganic pyrophosphatase 1), AQP5 (Aquaporin 5), and MT-ATP6 (Mitochondrially Encoded Adenosine Triphosphate Synthase Membrane Subunit 6). Furthermore, fluoride levels in the blood and urine were assessed using an ion-selective electrode, along with the evaluation of the inflammatory response in serum. The group with dental fluorosis exhibited 2.18 times higher MN frequencies specifically when assessed using the CBMN-Cyt assay, in comparison with individuals without fluorosis. Findings from the enzyme-modified comet assay indicated oxidative damage to purines in DNA. Furthermore, a decrease in TL was observed, along with elevated expression patterns of the PPA1 and AQP5 genes, and significant alterations in cytokine release. Significant correlations were identified between the TF and age, as well as the levels of necrotic cells. Additionally, noteworthy correlations were established between fluoride levels and the levels of MN, VS, and MT-ATP6. Although dental fluorosis results from fluoride exposure, our research highlights the potential influence of this condition on genomic instability and gene expression. Consequently, our findings stress the importance of continuously monitoring populations with a high incidence of dental fluorosis to enhance our comprehension of how genomic instability might correlate with the origins and consequences of health problems in these individuals.

Keywords: Dental fluorosis; Gene expression; Micronucleus; Mutagenicity tests; System biology; Telomere.