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Modification of circadian rhythms of drug metabolism in the Syrian hamster
Abstract:
Male Syrian hamsters consumed one of three levels of lactalbumin (10, 20, or 40%) for 8 weeks prior to administration of a single dose of 20 mg/kg (sc) N-nitrosobis(2-oxopropyl)amine (BOP) at 0600 hr. Liver weights, liver microsomal protein, and cytochrome P450 content and the activities of microsomal ethylmorphine N-demethylase (EMND), aniline hydroxylase (ANH), and arylhydrocarbon hydroxylase (AHH) were determined in control and BOP-treated animals after 0 (0600), 3 (0900), 6 (1200), 12 (1800), and 24 (0600) hr. Circadian rhythms were observed in liver weights, contents of microsomal protein, and cytochrome P450 and in the activities of EMND and ANH. Cycles of liver weight, cytochrome P450, and EMND activity were present in animals fed the higher (20 and 40%) lactalbumin levels, but not in those fed the low level (10%). BOP treatment eliminated the circadian cycles of cytochrome P450 and EMND, and reduced liver weight, the content of microsomal protein, and the ANH activity at two or three of the measurement times. AHH activity did not exhibit a circadian cycle, but these values were consistently increased by feeding high protein and reduced by BOP.