Døssing M
Int Arch Occup Environ Health. 1984;53(3):205-18. doi: 10.1007/BF00398814.
The activity of the hepatic microsomal enzyme system, which may be of great importance for metabolic activation and deactivation of hepatotoxic agents and carcinogens, is changed by exposure to commonly used industrial chemicals. The antipyrine test is the most widely used method for assessing microsomal enzyme activity in man. The clearance of antipyrine can be accurately calculated from one sample of saliva obtained about 24 h after an oral dose of the drug. By measuring antipyrine metabolism during exposure to industrial chemicals and at the end of 3-4 weeks free from exposure, the impact of industrial chemicals on antipyrine metabolism can be estimated, provided the chemicals are eliminated within 3-4 weeks. This test can be performed by skilled and unskilled workers using written instructions. This has broadened the application of the test. Other noninvasive indices of microsomal enzyme activity include the aminopyrine and caffeine breath tests and the urinary excretion of 6-beta-hydroxycortisol and D-glucaric acid. These tests probably reflect the activity of different but overlapping parts of the microsomal enzyme system and may be of value in research in occupational medicine. Previous studies indicate that chlorinated hydrocarbon insecticides, phenoxyacids, chlorophenols, polychlorinated biphenyles, some organic solvents and high concentrations of inhalation anaesthetics may stimulate microsomal enzyme activity, while styrene, toluene and inhalation anaesthetics in concentrations at about the allowed safety limit values have no effect. Lead, chemicals used by spray painters, and carbon disulphide probably inhibit the activity. While the short-term consequences of these changes include altered metabolism of hormones, vitamins, drugs, and other microsomally metabolized compounds, the possible impact on health on a long-term scale is unknown. It is now possible to study this with the use of the available noninvasive simple indices of microsomal enzyme activity. The potentially useful applications include biological monitoring of environmental carcinogenesis and hepatotoxicity.
肝微粒体酶系统的活性对于肝毒性药物和致癌物的代谢活化及失活可能极为重要,而接触常用工业化学品会改变该系统的活性。安替比林试验是评估人体微粒体酶活性最广泛使用的方法。口服该药后约24小时采集一份唾液样本,即可准确计算安替比林的清除率。通过测量接触工业化学品期间及脱离接触3 - 4周结束时的安替比林代谢情况,若化学品在3 - 4周内被清除,便可估算工业化学品对安替比林代谢的影响。该试验可由熟练和非熟练工人按照书面说明进行操作,这扩大了试验的应用范围。微粒体酶活性的其他非侵入性指标包括氨基比林和咖啡因呼气试验以及6 - β - 羟基皮质醇和D - 葡糖醛酸的尿排泄量。这些试验可能反映微粒体酶系统不同但相互重叠部分的活性,在职业医学研究中可能具有价值。先前的研究表明,氯代烃类杀虫剂、苯氧基酸、氯酚、多氯联苯、一些有机溶剂和高浓度的吸入麻醉剂可能会刺激微粒体酶活性,而苯乙烯、甲苯以及处于允许安全限值左右浓度的吸入麻醉剂则无影响。铅、喷漆工人使用的化学品以及二硫化碳可能会抑制其活性。虽然这些变化的短期后果包括激素、维生素、药物及其他经微粒体代谢的化合物代谢改变,但对长期健康可能产生的影响尚不清楚。现在利用现有的微粒体酶活性非侵入性简单指标来研究这一问题成为可能。其潜在的有用应用包括对环境致癌作用和肝毒性的生物监测。