Localization and age-related changes in cytochrome P450 expression in APA hamster livers

To establish the baseline data, age-related changes and the regional expres sion of the hepatic P450 isozymes in Syrian hamsters of the APA strain at 3 , 6 12, 18 months old were examined by immunological techniques. Immunohist ochemical analysis of liver serial sections revealed that the midzonal and perivenous regions (zones 2 and 3, respectively) were stained with the anti -rat CYP1A1/2, 2B1/2 and 2E1 antibodies. These three antibodies most intens ely stained the hepatocytes around the central vein. An anti-rat CYP3A2 sta ining section had a staining pattern with equally intense reactions in zone s 2 and 3. On the other hand, CYP2C6, 2C11 and 4A1 were distributed diffuse ly throughout the hepatic acinus. There was no age-related difference in th e expression pattern of any of the P450 isozymes examined. Total P450 conte nt had a peak at 6 months of age and decreased to 60% of that level thereaf ter. Western-blot analysis revealed that the peak expressions of the isozym es defected with anti-rat CYP1A1/2, 2C6, 2E1 and 3A2 antibodies were observ ed in 6-month-old hamsters and declined in older ones. The CYP2B and 2C11 c ontent reached the maximum at the age of 6 months and maintained almost the same level thereafter The CYP4A level did not change from 3 to 6 months, a nd then declined to about 40% of the younger level at 12 and 18 months of a ge. These results suggest that the hepatic P450 isozymes of APA hamsters ha ve region-specific expressions and most isozymes have their peaks of expres sion at 6 months of age, which differs from the patterns for rat P450.