Optimal fluoride treatment regimes have not yet been established, despite many years of investigation. Accordingly, the main aims of this thesis were (i) to develop an in vitro pH cycling model to investigate the effects of fluoride concentration on de-/ remineralisation and (ii) to further develop an in situ model for studying these factors in the natural oral environment. Microradiography and computerised microdensitometry were the techniques employed for assessing mineral content in human dental enamel sections. The first study showed no significant differences in demineralisation between bulk and thin sections of enamel. This was important as the ability to use thin enamel sections in de-/ remineralisation studies enables the mineral content to be measured, before, during and after the experiment, thereby overcoming the problem of inhomogeneity and enabling small changes in mineral content to be accurately assessed. Many laboratory systems are available for producing artificial subsurface carious lesions. In a comparative study, it was shown that solution-prepared artificial carious lesions were more responsive to de-/remineralisation processes than lesions prepared by a gelatin system and therefore better suited for studies incorporating the use of fluoride. For this reason, calcium phosphate solutions were used throughout this project to prepare subsurface lesions and to simulate de-/ remineralisation conditions. Current knowledge suggests that fluoride must be present in the aqueous phase to inhibit demineralisation and to enhance remineralisation. A pH cycling study incorporating pre-formed artificial carious lesions was employed to mimic the elevated baseline salivary fluoride levels which are known to be present in the mouth with frequent use of a fluoride agent (eg. pastes or rinses). The results showed that the pre-formed lesions responded significantly to increase in fluoride concentration in the remineralising solutions thus demonstrating the importance of frequency of fluoride application. The importance of the transient high fluoride levels, present in the mouth immediately after topical fluoride application were also investigated using in vitro pH cycling. A daily five minute exposure of the enamel specimens to neutral sodium fluoride solutions of different concentrations resulted in net remineralisation. However, solutions containing fluoride concentrations greater than 500 ppm did not produce any further significant increase in remineralisation, thereby indicating an optimium fluoride concentration at around 500 ppm. Much attention has recently been given to in situ studies which provide a natural environment for the study of caries preventive substances. The sensitivity of an in situ model was improved by using solution-prepared lesions which are more responsive than gelatin-prepared lesions, and by increasing the number of volunteers. This superior study allowed a fluoride dose-response relationship with sodium monofluorophosphate dentifrices to be demonstrated. In addition, significant differences between the two sides of the mouth could be measured as well as marked variations between volunteers in response to fluoridated and non-fluoridated pastes. The in vitro and in situ studies described in this project should be useful in complementing results from caries clinical trials which are the ultimate means of validating caries-preventive treatments
