Metabolizing systems in cell culture cytotoxicity tests.
1. The addition of 9000 g supernatant of rat liver homogenate (S9) or rat liver microsomal fractions to a cytotoxicity test system using BCL-D1 cells has been investigated. 2. The choice of culture medium influenced the intrinsic cytotoxicity of the metabolising system to the BCL-D1 cells. Use of Ham's F10 nutrient mixture resulted in greater cytotoxicity compared with several other media. 3. Microsomal fractions provided greater cytochrome P-450 dependent activation of cyclophosphamide and were less cytotoxic than S9. 4. Direct-acting toxic compounds, such as p-aminophenol, were less toxic in the presence of a metabolising system. This was due to protein-binding rather than enzymic detoxification.
Robens Institute of Industrial and Environmental Health and Safety, University of Surrey, Guildford, UK.
D J
DJ
Benford
H J
HJ
Reavy
S A
SA
Hubbard
D000171:Acrolein / Q000378:metabolism / Q000494:pharmacology; D000627:Aminophenols / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002729:Chloromercuribenzoates / Q000378:metabolism / Q000494:pharmacology; D002746:Chlorpromazine / Q000378:metabolism / Q000494:pharmacology; D003470:Culture Media; D003520:Cyclophosphamide / Q000378:metabolism / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D020245:p-Chloromercuribenzoic Acid
D000627:Aminophenols; D002729:Chloromercuribenzoates; D003470:Culture Media; D020245:p-Chloromercuribenzoic Acid; D000171:Acrolein; D003520:Cyclophosphamide; C026729:4-aminophenol; D002746:Chlorpromazine