[Evaluation of toxic doses of fluorine on expression of collagen genes and synthesis of some collagen proteins in rat skin].

The results of studies carried out over the last few decades indicate a significant involvement of fluoride in connective tissue metabolism. Unfortunately, opinions concerning this issue vary and sometimes are conflicting. Collagen constitutes the main component of the extracellular matrix. Biosynthesis of collagen is a complex, multistage process. Each step in collagen biosynthesis may be affected by exogenous factors. The purpose of the present study was to evaluate the effects of toxic doses of fluoride in drinking water on: 1. The level of COL1A1 gene expression in rat skin; 2. Concentrations of acid-soluble, pepsin-soluble and total collagen isolated from rat skin; 3. Ratio of pepsin-soluble to acid-soluble collagen concentrations; 4. Proportions of alpha2(I)/alpha1(I) and beta/alpha1(I) collagen chains in extracts ofpepsin-soluble collagen. An attempt was made to determine whether fluoride effects are gender-dependent. The experiment was performed in 108 Wistar rats (males and females). Rats were given 60 mg sodium fluoride/dm3 in drinking during 1, 3 or 6 months. Subsequently, animals were sacrificed and blood, femoral bones and fragments of abdominal skin were taken for analysis. Methods used in the study included potentiometry with F- ion-selective electrode, RT-PCR assay, calorimetry, and SDS-PAGE electrophoresis. The results led to the following conclusions: 1. COL1A1 gene expression in the skin of male rats receiving 60 mg NaF/dm3 in drinking water was significantly reduced after 6 months exposure. 2. Fluoride at doses used in the present study basically does not exert an effect on the concentration of each collagen form in rat skin, ratio of pepsin-soluble to acid-soluble collagen concentrations, and relative proportions of some collagen chains in the pepsin-soluble collagen extract. 3. Male rats were more sensitive to fluoride action in the present study as compared with females. 4. Further research on fluoride penetration to the skin in experimental animals is needed in order to elucidate the relatively low toxicity of fluoride in this tissue.