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Abstract:
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.
Insights
This study demonstrates that in vitro cytotoxicity testing accurately predicts chemical toxicity in vivo. Comparing cell culture results with animal studies validates this approach for evaluating drug safety and developing new toxicology methods.
Area of Science:
- Toxicology
- Cell Biology
- Drug Discovery
Background:
- Traditional toxicity screening relies on less differentiated cell cultures.
- Organ-specific cell cultures predict drug action on specific body targets.
- Existing methods assess chemical cytoinhibitory effects for antineoplastic and local irritation prediction.
Purpose of the Study:
- To establish the relevance of in vitro screening in tissue culture for predicting chemical toxicity.
- To develop a screening model comparing in vitro cytotoxicity with in vivo toxicity.
- To evaluate the systemic cytotoxicity of chemicals and combined compound toxicity.
Main Methods:
- Screening chemicals and fermentation broths for cytoinhibitory effects.
- Testing metal and plastic materials for cytoinhibitory effects.
- Assessing mutagenicity and transformation capacity of chemicals in tissue culture.
- Comparing in vitro cytotoxicity with in vivo toxicity data for 85 drugs.
- Screening combinations of cytotoxic compounds for combined systemic toxicity in vitro.
Main Results:
- In vitro cytotoxicity strongly correlates with systemic lethal action for most tested drugs.
- A validated screening model allows for the evaluation of systemic cytotoxicity.
- In vitro screening of compound combinations predicts their combined systemic toxicity.
Conclusions:
- In vitro cytotoxicity testing is a relevant and predictive method for assessing chemical toxicity.
- The study supports the development of in vitro cytotoxicology as a subdiscipline of toxicology.
- This approach enhances the prediction of drug safety and potential adverse effects.