Ontogenetic expression of polycyclic aromatic compound inducible monooxygenase activities and forms of cytochrome P 450 in rabbit. Evidence for temporal control and organ specificity of two genetic regulatory systems

S. A. Atlas, A. R. Boobis, J. S. Felton, S. S. Thorgeirsson, D. W. Nebert

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Abstract

Developmental curves of liver microsomal cytochrome P-450 total content and five monooxygenase activities from control and 3-methylcholanthrene-treated New Zealand White rabbits were determined from 5 days prior to birth to adulthood (110 days of age). Microsomes were concomitantly analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. N-Acetylarylamine (2-acetylaminofluorene) N-hydroxylase induction by 3-methylcholanthrene parallels quite closely increases in an electrophoretic band of 54,000 daltons and the approximately 2 nm spectral shift to the blue in the Soret peak of the reduced hemoprotein.CO complex, and the induced N-hydroxylase activity is markedly inhibited by α-naphthoflavone in vitro; these parameters develop in rabbits of age 10 days and older. Biphenyl 4-hydroxylase induction by 3-methylcholanthrene is at least 2-fold in the fetus and neonate for the first 10 days of age, is less than 2-fold between 16 and 40 days of age, and is absent in rabbits 50 days and older. Aryl hydrocarbon (benzo[a]pyrene) hydroxylase induction and biphenyl 2-hydroxylase induction by 3-methylcholanthrene, as well as detectable basal levels of biphenyl 2-hydroxylase activity, exist in the fetus and neonate 12 days old or younger but not in the older animal. These parameters are associated with increases in an electrophoretic band of 57,000 daltons, the absence of an hypsochromic spectral shift in the Soret maximum of the reduced hemoprotein.CO complex, and marked sensitivity of 3-methylcholanthrene-induced aryl hydrocarbon hydroxylase to α-naphthoflavone inhibition in vitro. An increase in an electrophoretic band of 60,000 daltons exists in 3-methylcholanthrene-treated rabbits of age 5 days before birth but not in any of the older 3-methylcholanthrene-treated rabbits. 7-Ethoxycoumarin O-deethylase activity is induced by 3-methylcholanthrene in the fetus and neonate 10 days old or younger but is decreased 40 to 60% by 3-methylcholanthrene treatment in vivo at all ages beyond 10 days; this decreased activity closely parallels decreases in an electrophoretic band of 50,000 daltons in these 3-methylcholanthrene-treated animals. In contrast, phenobarbital principally increases the electrophoretic band of 50,000 daltons and causes smaller increases in bands of 47,000, 54,000 and 57,000 daltons in the liver of adult rabbits. 3-Methylcholanthrene induces aryl hydrocarbon hydroxylase in rabbit kidney, lung, and spleen of neonatal rabbits. In contrast to the hepatic and lung enzymes, however, kidney and spleen hydroxylase activities remain inducible by 3-methylcholanthrene throughout adulthood. In these nonhepatic tissues, an increase in only the electrophoretic band of 57,000 daltons occurs, which is always associated with the induced hydroxylase activity and which is not associated with a blue spectral shift in the Soret peak of the reduced hemoprotein.CO complex.

Original languageEnglish
Pages (from-to)4712-4721
Number of pages10
JournalJournal of Biological Chemistry
Volume252
Issue number13
StatePublished - 1977
Externally publishedYes

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