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Biomedical subjects

A H Conney

Publications and source records attributed to A H Conney.

324 records · Page 18Linked to original sources
PubMedDate not supplied

Effect of 3-methylcholanthrene treatment on phenacetin O-dealkylation in several inbred mouse strains.

An increase in the metabolism of phenacetin to N-acetyl-p-aminophenol is correlated with benzo[a]pyrene hydroxylase induction by 3-methylcholanthrene among several inbred mouse strains. While the magnitude of induction of phenacetin O-dealkylation is considerably less than that of benzo[a]pyrene hydroxylation, the data indicate that in mice, the metabolism of these two substrates is under similar regulatory control.

Animals↗
PubMedDate not supplied

Effects of three recombinant human leukocyte interferons on drug metabolism in mice.

Three recombinant human leukocyte interferons (IFLrA, IFLrD, and a hybrid IFLrA/D) that differ markedly in their antiviral activity in murine L cells were examined for their effects on hepatic microsomal drug metabolism in adult female CD-1 mice. When administered for 1 or 3 consecutive days, IFLrA/D, which exhibited the highest antiviral activity in murine L cells, caused a dose-dependent decrease in cytochrome P-450 content and in the rate of metabolism in vitro of benzo[a]pyrene, hexobarbital, 7-ethoxycoumarin, benzphetamine, and zoxazolamine. The concentration of cytochrome b and the activity of NADPH-cytochrome c reductase were also depressed when IFLrA/D was administered for 3 days. Similar but somewhat smaller changes were observed following treatment of mice with IFLrD, which possessed approximately 1% of the antiviral activity of IFLrA/D in murine L cells. In contrast, IFLrA, which was essentially devoid of antiviral activity in the mouse cell line, failed to depress cytochrome P-450 levels and in vitro drug metabolism activity in a consistent or dose-dependent manner. Cytochrome P-450 content and the in vitro rate of metabolism of benzphetamine and zoxazolamine were maximally depressed 8-24 hr after a single intraperitoneal injection of 1.5 micrograms of interferon per mouse; at this time the interferons were no longer detectable in serum. Near-normal levels of cytochrome P-450 and in vitro drug metabolism activity were restored by 48 hr after a single injection of interferon. Treatment of mice with 1.5 micrograms of IFLrA/D once daily for 3 days prolonged hexobarbital sleeping time but not zoxazolamine paralysis time, whereas neither of these was influenced by treatment with IFLrA or D. The results indicate that an interferon-dependent process reduces the level of microsomal cytochrome P-450 in liver and potentiates the pharmacological actions of certain drugs in mice.

Animals↗
PubMedDate not supplied

Effects of betamethasone on the in vitro and in vivo 2-hydroxylation of biphenyl in the rat.

The in vitro addition of betamethasone to rat liver microsomes caused a concentration-dependent stimulation of biphenyl 2-hydroxylation. At a 100 microM concentration of betamethasone, the formation of 2-hydroxybiphenyl was increased by approximately 4-fold in microsomes from 28-day-old rats and 10-fold in liver microsomes from 5-day-old rats. The steroid had little or no effect on the hydroxylation of biphenyl in the 3- or 4-position except at the highest concentration tested (1 mM), where a 20-30% inhibition was observed. The ip injection of 0.01 to 10 mumol of betamethasone to 5-day-old rats had little or no effect on the total body metabolism of 0.01 to 3.5 mumol of biphenyl-2-3H to 2-hydroxybiphenyl as measured by 3H2O formation. Although betamethasone had no effect on the 2-hydroxylation of biphenyl in the intact rat, this reaction was stimulated 4- to 9-fold by the addition of 100 microM betamethasone to hepatocyte monolayer cultures.

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