Screening of toxic compounds in tissue culture.

To screen toxicity of chemicals most often easily manageable cultures of less differentiated cells have been used. This work includes 3 fields: (i) Screening of chemicals and fermentation broths for their cytoinhibitory effect, to predict antineoplastic activity. A related practical approach is to achieve optimal antitumour drug therapy by testing drugs on cultures of tumour cells from the patient. (ii) Screening of metal and plastic materials used in medicine, surgery and dentistry for their cytoinhibitory effect to predict local irritation. (iii) Screening of the mutagenicity or transformation capacity of chemicals in tissue culture, to predict their carcinogenicity. In addition, organ-specific cultures of most specialized cells (hepatocytes, ova, nerve cells, heart cells, skin cells, respiratory mucosa, and macrophages) have also been used to predict drug action on corresponding targets in the body. The author's group has focused on 2 new uses of standard cells for screening chemical toxicity: (i) Comparisons of in vitro cytotoxicity with in vivo toxicity of 85 randomly selected drugs indicated that for most drugs a systemic lethal action was brought about by cytotoxicity. A screening model is advocated by which results of cytotoxicity tests are compared with systemic toxicity in vivo to evaluate the systemic cytotoxicity of chemicals. (ii) Combinations of compounds with a cytotoxic lethal action in man indicated by the previous method have been screened in vitro for their combined systemic toxicity. By systematic comparison of results from standardized in vitro tests with in vivo toxicity, steps have been taken to resolve the question of the relevance of screening in tissue culture and to contribute to the development of an emerging subdiscipline to toxicology -- in vitro cytotoxicology.