[Induction of cytochrome P450 2A5 in transplanted mouse hepatoma]

We have studied selective induction in vivo isoform of cytochrome P4502A in mouse hepatomas. Activity of coumarin 7-hydroxylase was increased in hepatoma 61 following pyrazole and cobalt chloride treatment. Microsomes isolated from hepatoma 61 transplanted to mice treated with either pyrazole or cobalt chloride catalyzed oxidation of coumarin and 7-ethoxycoumarin at rates 2-2.5-fold higher than in saline controls. Western blot analysis of hepatoma microsomes showed that the increase in functional activity of coumarin 7-hydroxylase was due to induction of CYP2A5 (cytochrome P450 isoenzyme catalysing coumarin 7-hydroxylation). Pyrazole or cobalt chloride induced the enzyme activity in hepatoma 61, whereas we did not measure induction of CYP2A5 in hepatoma 60. The changes in the amount of CYP2A5 in liver were more pronounced after pyrazole treatment than that after cobalt. It is suggested that hepatomas 60 and 61 are originated through initiation of hepatocytes which are localized within different regions of liver lobule.