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Biomedical subjects

A H Conney

Publications and source records attributed to A H Conney.

At least 271 records · Page 15Linked to original sources

Metabolic interactions among environmental chemicals and drugs.

It is evident that metabolic interactions can occur among drugs, insecticides, food additives, carcinogenic hydrocarbons, and a variety of environmental chemicals. A common denominator governing these effects is the versatile nature of the liver microsomal enzymes that metabolize chemicals with diverse structures and biological activities, and the fact that these enzymes can be stimulated or inhibited by other chemicals administered simultaneously. The discovery of these particular enzymes in the 1950's laid the groundwork for the current research on metabolic interactions. Such research provides information that is helpful in the evaluation of the safety and efficacy of drugs and environmental chemicals, and suggests new directions for further research. Some examples are as follows.

Animals↗

Induction of benzo( )pyrene hydroxylase in human skin.

Foreskins from children who were circumcised 2 to 4 days after birth contain an enzyme system that hydroxylates the carcinogen benzo[alpha]pyrene. When foreskin was cultured for 16 hours in the presence of 10 micromolar benz[alpha]anthracene, a two- to fivefold increase in activity of benzo[alpha]pyrene hydroxylase was obtained. An evaluation of the basal activity and inducibility of carcinogen-metabolizing enzymes in human tissues may provide a means of determining the ability of different individuals to metabolize carcinogens.

Benz(a)Anthracenes↗

Decreased concentration of phenacetin in plasma of cigarette smokers.

The amount of phenacetin in plasma was determined in nine control subjects (nonsmokers) and nine subjects who smoked at least 15 cigarettes per day. The mean plasma concentration of phenacetin at 1, 2, 3(1/2), and 5 hours after its administration was markedly lower in cigarette smokers than in nonsmokers. At 2 hours after the oral administration of 900 milligrams of phenacetin, the plasma concentration (+/- standard error) of unchanged drug was 2.24 +/- 0.73 micrograms per milliliter in the controls and 0.48 +/- 0.28 micrograms per milliliter in the smokers. The rate of excretion in urine of the major metabolite of phenacetin, N-acetyl-p-aminophenol, was the same in both groups. These results indicate for the first time decreased concentrations of a drug in plasma of persons who smoke cigarettes, and the results suggest that the decrease in the amount of Phenacetin in plasma may result from increased metabolism of phenacetin in cigarette smokers.

Acetaminophen↗