Cytochromes P‐450 and bs in human liver microsomes

Alvares, Alvito P.; Schilling, G.; Levin, Wayne; Kuntzman, R.; Brand, Leonard; Mark, Lester C.

doi:10.1002/cpt1969105655

Cited by 69 publications

(23 citation statements)

References 5 publications

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“…As expected (15, 28), 3-MeChol had no effect on the activity of ethylmorphine N-demethylase; however, Aroclor treatment (Table 2) resulted in a significant enhancement of N-demethylase activity, though of a lesser magnitude than that observed in rats treated with phenobairbital. The data obtained with 3-MeChol and phenobarbital are similar to those previously reported (14,15,28,29).…”

Section: Resultssupporting

confidence: 89%

Polychlorinated Biphenyls: A New Type of Inducer of Cytochrome P-448 in the Liver

Alvares

Bickers

Kappas

1973

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

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188

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The CO-difference spectrum of microsomes from rats treated with the polychlorinated biphenyls mixture, Aroclor 1254, has an absorption maximum at 448 nm. With ethylisocyananide as the ligand for reduced microsomes, Aroclor 1254 treatment causes a shift in the 455-nm peak to 453 nm and increases the ratio of absorbance of 455 nm to that at 430 nm from 0.53, obtained with untreated rats, to 1.24. These findings are similar to those seen in rats treated with the polycyclic hydrocarbon, 3-methylcholanthrene, but differ from those that characterize cytochrome P-450 in control or phenobarbitaltreated rats. Aroclor 1254 treatment results in a tripling of cytochrome P-448 content and a 10-fold increase in benzo-[alpyrene hydroxylation. However-unlike 3-methylcholanthrene, but like the phenobarbital type of inducing agents-Aroclor 1254 treatment causes a significant enhancement of ethylmorphine N-demethylase. These data suggest that Aroclor 1254-induced cytochrome P-448 may be catalytically different from the 3-methylcholanthreneinduced P-448 or that the hemoprotein(s) induced by Aroclor 1254 may be a mixture of cytochromes P-448 and P-450 exhibiting catalytic properties of both cytochromes.

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Section: Resultssupporting

confidence: 89%

Polychlorinated Biphenyls: A New Type of Inducer of Cytochrome P-448 in the Liver

Alvares

Bickers

Kappas

1973

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

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188

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“…In man, the activity of drug-metabolizing enzymes in the liver can be assayed directly from samples taken during surgery or by percutaneous needle biopsy (Alvares, Schilling, Levine, Kuntzman, Brand & Mark, 1969;Billing & Black, 1971;Thorgeirsson, 1971;Schoene et al, 1972;May et al, 1974). We utilized a Thrucut needle for percutaneous biopsy obtaining enough material for both histological studies and determination of cytochrome P-450.…”

Section: Calculationsmentioning

confidence: 99%

Drug metabolism in epileptics: in vivo and in vitro correlations.

Ea¹,

Pelkonen²,

Ahokas³

et al. 1978

Brit J Clinical Pharma

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I The effect of inducing drug therapy on the relationship between in vitro (cytochrome P-450 content) and in vivo (antipyrine kinetics) was investigated by comparing eleven consecutively treated epileptics with two groups of controls, eleven subjects with normal liver histology and eleven disease matched non-epileptics, all underwent diagnostic liver biopsy. 2 The epileptics had significantly higher cytochrome P-450 level in biopsies and they also metabolized antipyrine taster than the controls. 3 Decrease in antipyrine half-life in epileptics was related with alterations in liver histology, whereas the level of cytochrome P-450 was not. 4 There was a linear relationship between these two indices of enzyme induction when regressed on logarithmic data.

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“…Because phenobarbital induces preferentially the cytochrome P4W system (11,12), we have treated jaundiced Gunn rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent known inducer of microsomal cytochrome P448 (P1450) (13), to determine its effect on metabolism of unconjugated bilirubin.…”

mentioning

confidence: 99%