The effect of β-naphthoflavone on rabbit liver protein synthesis, and on the induction of cytochrome P-450 LM4 mRNA

Nash, Kevin L.; Chiang, John Y.L.; Steggles, Alan W.

doi:10.1016/0006-291x(81)91938-0

Cited by 6 publications

(2 citation statements)

References 10 publications

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“…3) are comparable to those reported for adult chickens and other animals (10,(37)(38)(39)(40)(41). 8NF has been reported to be a potent inducer of AHHase activity in other species (42,43). Although the effective dose range for /3NF was similar to that for 3MC in the chicken embryo (Fig.…”

Section: Discussionsupporting

confidence: 71%

Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo.

Hamilton

Denison

Bloom

1983

Proc. Natl. Acad. Sci. U.S.A.

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The development of the hepatic microsomal mixed-function oxidase system was studied to determine the basal level of embryonic enzyme activity and the inducibility of this system throughout growth and differentiation. Chicken embryo livers were assayed for basal and inducible hepatic aryl hydrocarbon hydroxylase (AHHase; designated elsewhere as AHH) activity from the first appearance of the liver as a discrete organ at 5 days of incubation (DI) through day 10 after hatching. In addition, wholeembryo and viscera preparations were assayed at 3 and 4 DI. Basal AHHase activity was equal to or greater than adult levels from 3 DI through hatching in all preparations (approximately 0.3-0.5 nmol/min per mg). A 3-fold increase in basal activity above adult values occurred at hatching. The onset of inducibility in chicken embryo liver between 5 and 6 DI was concomitant with hepatocyte differentiation. A developmental profile of 24-hr 3,4,3',4'-tetrachlorobiphenyl-induced AHHase activity showed 15-to 30-fold induction over controls from 7 DI through day 10 after hatching, with a maxmum of 15 nmol/min per mg at 14 DI and day 1 after hatching, a specific activity >50% greater than maximal induction in the adult. Embryonic AHHase activity was also induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, 3-naphthoflavone, and sodium phenobarbital. Induction kinetics throughout embryonic development were similar to those reported for the adult chicken and other animals. These findings demonstrate development of a mixed-function oxidase system in very early embryogenesis and then in the liver as it differentiates. Liver AHHase activity is inducible throughout development and perinatally but such activity is under strict developmental regulation. The chicken embryo has adult levels of AHHase activity which would be sufficient to achieve metabolic activation of promutagens /carcinogens before and after hepatocyte differentiation.The chicken embryo is a sensitive indicator of the teratogenic (1) and mutagenic (2) capacity of xenobiotics. Since its development as the first in vivo sister chromatid exchange (SCE) assay (3), it has been used to screen more than 50 compounds for mutagenic activity, including both direct-and indirect-acting compounds (4, 5). The induction of SCEs at 3 days of incubation (DI) by compounds known to require activation to mutagenic metabolites indicates the presence of a xenobiotic-metabolizing system very early in chicken embryo development (4, 5). Furthermore, there was an increase in the frequency of SCEs at 6 DI from the same dose of an indirect-acting mutagen/carcinogen compared to the SCE frequency at 3 DI, in spite of a 17-fold increase in embryo weight, whereas the same dose of direct-acting mutagen at 6 DI as at 3 DI caused a decrease in SCEs in the older embryo (6). This differential response between 3 DI and 6 DI potentially could be explained by either an increase in basal enzyme levels or an increased inducibility of xenobiotic-metabolizing enzymes.Drummond et aL (7) report...

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Section: Discussionsupporting

confidence: 71%

Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo.

Hamilton

Denison

Bloom

1983

Proc. Natl. Acad. Sci. U.S.A.

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“…Alternatively the rate limiting step in the biosynthesis of cytochrome P-450 may involve a post translational process such as heme insertion into the newly synthesised apoprotein. This is indeed conceivable as it is known that the apoprotein of cytochrome P-450 and the heme group turn over at different rates in vivo (107) and the presence of spectrophotometrically detectable cytochrome P-450 as described for PB induction, it is interesting to note that the induction of cytochrome P-450 by BNF as measured in the cell free system follows a similar temporal pattern (92). Lechner and Sinogas (94) have suggested that the time course of the nuclear pre-mRNA processing into functional polyadenylated mRNA and its subsequent expression following induction by PB may be modulated by the presence of messenger ribonucleoprotein particles (RNP's).…”

Section: Biosynthesis Of Cytochrome P-450 Directed By Rat Liver Messementioning

confidence: 88%