Toxicity of precocene II in rat hepatocyte cultures: effects of serum and culture time.
Omission of serum from culture medium markedly increased the toxicity of the cytochrome P450-activated toxin precocene II in 24-h cultures of rat hepatocytes. In addition, the depletion of glutathione and inhibition of cytochrome P450 in 24-h cultures increased and decreased, respectively, the toxicity of precocene II, as seen in vivo. Precocene II was also toxic to 72-h cultures, although the effect of the serum-free medium was attenuated. However, depletion of glutathione and inhibition of P450 had little or no effect on the toxicity in 72-h cultures. Therefore, the mechanism of precocene II-induced cell death appears to change with time in culture.
Hammond
A H
AH
Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, UK.
Fry
J R
JR
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001578:Benzopyrans / Q000633:toxicity*; D019328:Buthionine Sulfoximine; D002478:Cells, Cultured; D003470:Culture Media; D016895:Culture Media, Serum-Free; D065607:Cytochrome P-450 Enzyme Inhibitors; D005978:Glutathione / Q000037:antagonists & inhibitors; D007306:Insecticides / Q000633:toxicity*; D007605:Juvenile Hormones / Q000037:antagonists & inhibitors*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D010944:Plants; D051381:Rats; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
D000963:Antimetabolites; D001578:Benzopyrans; D003470:Culture Media; D016895:Culture Media, Serum-Free; D065607:Cytochrome P-450 Enzyme Inhibitors; D007306:Insecticides; D007605:Juvenile Hormones; D014230:Triazoles; C033020:1-aminobenzotriazole; D008717:Methionine Sulfoximine; C014163:precocene II; D019328:Buthionine Sulfoximine; D005978:Glutathione