Cytochrome P-450 deficiency and resistance to t-butyl hydroperoxide of hepatoma microsomal lipid peroxidation.
Lipid peroxidation of microsomes from rat liver and Morris hepatoma 9618A was induced by means of tert-butyl hydroperoxide (t-BuOOH). In rat liver microsomes t-BuOOH stimulated an early formation of lipid hydroperoxides (LOOH) and an increasing accumulation of malondialdehyde; t-BuOOH was completely consumed and cytochrome P-450 was rapidly destroyed. In hepatoma microsomes (60% deficiency of cytochrome P-450) a remarkable inhibition of both malondialdehyde and LOOH was observed; t-BuOOH was consumed only partially and cytochrome P-450 was destroyed slowly. In the presence of aminopyrine, malondialdehyde production was inhibited to the same extent (about 70%) in normal and tumour microsomes. The concentration of t-BuOOH required to achieve half-maximal velocity of malondialdehyde accumulation was comparable in the two microsome types. It is proposed that the deficiency of cytochrome P-450 limits the activation of t-BuOOH to the free radical species which initiate lipid peroxidation. Low cytochrome P-450 content would also affect the LOOH-dependent propagation of lipid peroxidation.
D000818:Animals; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D010545:Peroxides / Q000494:pharmacology*; D051381:Rats; D011912:Rats, Inbred ACI; D011915:Rats, Inbred BUF; D014810:Vitamin E / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D008054:Lipid Peroxides; D010545:Peroxides; D014810:Vitamin E; D003577:Cytochrome P-450 Enzyme System; D020122:tert-Butylhydroperoxide