Interest in the effects of electric fields on biological tissues has been motivated by the natural occurrence of fields within tissues, which suggests that they may play a role in physiological function. The possibility that applied electric fields may alter physiological function, either in a beneficial or harmful way, has raised further significant interest.

In this thesis, the issue of the effect of electric fields on biological tissues was addressed using field-induced changes in stress protein and total protein synthesis in cartilage tissue as an experimental model. In cartilage, electric fields and currents are generated during physiological loading. The amplitudes and frequencies of the applied fields were motivated by the values associated with the naturally occurring fields, and by some models of possible mechanisms of interaction. Synthesis of stress proteins is induced by a variety of toxic agents. Therefore, it is an appropriate marker for stress induced by applied fields over a wide range of frequencies, in which several mechanisms of interaction might be important. Total protein synthesis serves as a marker for a generalized field-induced change in cellular metabolism.

Culture conditions for the cartilage tissue were chosen with a view to op timizing the sensitivity of stress and total protein synthesis to a stimulus such as the electric field, and to produce steady state protein synthesis prior to electrical stimulation. The response to heat, a stimulus known to produce a stress response was used to examine the sensitivity of cartilage to a stimulus under a variety of culture conditions-different serum concentrations and days of culture.

Cartilage specimens were exposed to current densities up to 30 mA frequencies of 1, 10, and 100 Hz and 1 and 10 kHz for 12 hours in a chamber filled with media containing 35 S-methionine. Unstimulated controls were incubated and labelled in an identical specimen chamber in the same incubator. Protein synthesis in electrically stimulated specimens relative to controls was assessed. Stress protein synthesis was assessed by examination of gel fluorographs. Total protein synthesis was assessed by radiolabel incorporation.

No stress protein synthesis was induced for current densities up to 30mA/cm², at frequencies of 1,10, and 100 Hz and 1 and 10 kHz. This lack of stress response indicates that felds within these amplitudes and frequencies are not toxic to cartilage tissue, in the sense defined by the stress response. The maximum current density applied was at least an order of magnitude larger than fields ap plied clinically, and is many orders of magnitude larger whan fields expected to be induced by environmental sources for frequencies less than 10 kHz. Therefore, these experiments do not suggest possible hazardous effects of electric fields which would be associated with synthesis of stress proteins.

An increase in total protein synthesis, as measured by 35S-methionine incor poration, was induced for high enough current densities (>10 mA/cm). Electric fields, therefore, appear to act by some mechanism to change au important physi ological function of the chondrocytes. The increase in incorporation depended on the position on the joint surface from which plugs were obtained, which resulted in a large variation in the response to electric fields within a single experiment. The mean increase in incorporation, however, increased with the magnitude of the current density.

The finding that relatively large current densities were required to measurably increase protein synthesis does not necessarily indicate that physiological current densities are unimportant. This model system displayed enough variation that small changes in synthesis (e.g. <20%) were difficult to quantify. Such small changes can be important, particularly if the change occurs in a few specific proteins or over a long period of time.

The change in total protein synthesis indicates that electric fields may play a role in physiological regulation of chondrocyte metabolism. These results may have important implications regarding clinical applications of fields to alter growth and remodeling.