The contribution of cytochemistry and electron microscopy to the detection of contaminants in the cell material used for the production of virus vaccines.

For the production of virus vaccine it is essential to use cellular material free of contaminants that could reach the final product. It is also important to check initial tissue for possible inherent infections. Studies on primary culture of chick embryo fibroblasts have shown in several cases that cultures which appeared normal by current cytological methods had a strongly positive reaction when investigated by the Feulgen reaction for nuclear DNA and acridine orange method proving intense RNA synthesis. Comparison of electron microscopic (EM) pictures of cell sections with results obtained from negatively stained preparations of identical cell material after pronase digestion have shown the presence of viruses, thus elucidating the nature of the inclusions. The combined approach of the above-mentioned problem by cytochemical and EM methods can usefully enlarge the rage of tests employed for the definition of cell populations acceptable for virus vaccine production.