Reaction products (adducts) of acrylamide with N termini of hemoglobin (Hb) are regularly observed in persons without known exposure. The average Hb adduct level measured in Swedish adults is preliminarily estimated to correspond to a daily intake approaching 100 μg of acrylamide. Because this uptake rate could be associated with a considerable cancer risk, it was considered important to identify its origin. It was hypothesized that acrylamide was formed at elevated temperatures in cooking, which was indicated in earlier studies of rats fed fried animal feed. This paper reports the analysis of acrylamide formed during heating of different human foodstuffs. Acrylamide levels in foodstuffs were analyzed by an improved gas chromatographic−mass spectrometric (GC-MS) method after bromination of acrylamide and by a new method for measurement of the underivatized acrylamide by liquid chromatography−mass spectrometry (LC-MS), using the MS/MS mode. For both methods the reproducibility, given as coefficient of vari...

Analysis of Acrylamide, a Carcinogen Formed in Heated Foodstuffs

Toxic oxygen free radicals have been implicated as important pathologic mediators in many clinical disorders. We discuss the chemistry of oxygen radical production and the roles of iron an...

Oxygen Radicals and Human Disease

Bipyridine: the most widely used ligand. A review of molecules comprising at least two 2,2'-bipyridine units.

Cigarette smoking remains highly prevalent in most countries. It can affect drug therapy by both pharmacokinetic and pharmacodynamic mechanisms. Enzymes induced by tobacco smoking may also increase the risk of cancer by enhancing the metabolic activation of carcinogens. Polycyclic aromatic hydrocarbons in tobacco smoke are believed to be responsible for the induction of cytochrome P450 (CYP) 1A1, CYP1A2 and possibly CYP2E1, CYP1A1 is primarily an extrahepatic enzyme found in lung and placenta. There are genetic polymorphisms in the inducibility of CYP1A1, with some evidence that high inducibility is more common in patients with lung cancer. CYP1A2 is a hepatic enzyme responsible for the metabolism of a number of drugs and activation of some procarcinogens. Caffeine demethylation, using blood clearance or urine metabolite data, has been used as an in vivo marker of CYP1A2 activity, clearly demonstrating an effect of cigarette smoking, CYP2E1 metabolises a number of drugs as well as activating some carcinogens. Our laboratory has found in an intraindividual study that cigarette smoking significantly enhances CYP2E1 activity as measured by the clearance of chlorzoxazone. In animal studies, nicotine induces the activity of several enzymes, including CYP2E1, CYP2A1/2A2 and CYP2B1/2B2, in the brain, but whether this effect is clinically significant is unknown. Similarly, although inhibitory effects of the smoke constituents carbon monoxide and cadmium on CYP enzymes have been observed in vitro and in animal studies, the relevance of this inhibition to humans has not yet been established. The mechanism involved in most interactions between cigarette smoking and drugs involves the induction of metabolism. Drugs for which induced metabolism because of cigarette smoking may have clinical consequence include theophylline, caffeine, tacrine, imipramine, haloperidol, pentazocine, propranolol, flecainide and estradiol. Cigarette smoking results in faster clearance of heparin, possibly related to smoking-related activation of thrombosis with enhanced heparin binding to antithrombin III. Cutaneous vasoconstriction by nicotine may slow the rate of insulin absorption after subcutaneous administration. Pharmacodynamic interactions have also been described. Cigarette smoking is associated with a lesser magnitude of blood pressure and heart rate lowering during treatment with beta-blockers, less sedation from benzodiazepines and less analgesia from some opioids, most likely reflecting the effects of the stimulant actions of nicotine. The impact of cigarette smoking needs to be considered in planning and assessing responses to drug therapy. Cigarette smoking should be specifically studied in clinical trials of new drugs.

Freddie W. Best

Papers

Smoke composition. An extensive investigation of the water-soluble portion of cigarette smoke

Etching and deactivating glass capillary columns for gas chromatography