Enhancement of microsomal drug hydroxylation and glucuronidation in rat liver by phenobarbital and 3-methylcholanthrene in combination.
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Biomedical subjects
Publications and source records attributed to A Aitio.
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Biomonitoring was developed for the assessment of the health risks from exposure to chemicals at work, and the approaches and concepts of biomonitoring are derived from such exposures. At present, biomonitoring is increasingly used also to assess exposure from the environment. Biomonitoring and assessment of external exposure are complementing activities, where the exposure assessments are much more widely applied, especially when the number of chemicals concerned is considered; environmental analysis also offers the distinct advantage of speciation analysis--which is very poorly developed for biomonitoring. Biomonitoring on the other hand provides information on exposure from all sources, and via all absorption routes, and considers also accumulation of the chemical in the body. Bio monitoring using exposure biomarkers thus consider interindividual differences in the absorption, while use of effec biomarkers ideally also considers interindividual differences in sensitivity. Few effect biomarkers, however, have been validated. The major challenges of biomonitoring are the development of monitoring methods, which are inexpensive enough to be applied at a frequency that makes possible meaningful biomonitoring of chemicals with a short half-time; development of exposure biomarker guidance values specific to individual species of different metals; ex pansion of the repertoire of validated effect biomarkers; and validation and application to effect monitoring of the omic technologies. Another major challenge is a reconsideration of the basis of biomonitoring action limits to reflec the change in the work place: Biomonitoring should be adapted to assist in the generation of a healthy workplace which is capable of attracting workers, and assist them to perform their work effectively--rather than just to guarantee absence of serious health effects.
The stereoselectivity of cytosolic glutathione S-transferases (GS-T) in rat tissues was determined using (+/-)-benzo(a)pyrene 4,5-oxide (BPO), (+/-)-benz(a)anthracene 5,6-oxide (BAO), pyrene 4,5-oxide (PO), and (+/-)-styrene 7,8-oxide (SO) as substrates. An HPLC system is described which separates the four diastereomeric glutathione (GSH) adducts of BPO. Liver, lung, testis, and heart cytosol were found to be highly selective for catalysis of the reaction of the GSH sulfur atom with R-configured oxirane carbon atoms of BPO; heart was the most stereoselective of these tissues with 93% of the products arising from thiol attack at the R-configured carbons. These same tissues showed identical but lower stereoselectivity with PO or BAO as substrate. With SO as substrate, GSH attack was primarily at the benzylic carbon atom of the R-configured enantiomer in all tissues. In contrast, kidney and spleen cytosol were highly stereoselective for reaction of GSH with S-configured oxirane carbon atoms of all three polycyclic arene oxides (R/S ratio = 0.2-0.3) and showed a greater amount of attack at the terminal carbon atom of (7R)-SO. Enantioselectivity of GS-T from these tissues with BPO as substrate varied substantially; liver, kidney, spleen, and intestine preferentially catalyzed reaction with (4R,5S)-BPO (2.8- to 5.1-fold), but testis, lung, and heart showed little or no enantioselectivity [(4R,5S)-BPO/(4S,5R)-BPO = 1.3, 1.3, and 0.96, respectively]. In general, the differences in stereoselectivity between different rat tissues correlate with known tissue differences in isozyme composition and demonstrate that some rat GS-T isozymes may have markedly different stereo- and enantioselectivities with chiral epoxide substrates.
A quality control program of analyses of toxic metals in urine has been carried out in the Nordic countries since 1978. In connection with these programs, the advantages and disadvantages of lyophilized compared to natural urine specimens as control materials have been investigated in three successive similar studies. Three parallel lyophilized and natural specimens were distributed to 12 participating laboratories. Two of the three specimen pools were spiked with known amounts of As, Cd, Cr, Hg, Ni, and Pb standard solutions. The data indicate no clear differences in the mean concentrations, coefficients of variation, or mean recoveries for the various metals between the two control materials used with the various types of analytes. However, rather wide random variations were observed, emphasizing the analytical difficulty of these analyses and the need for routine quality control.
Exposure to at least 100 different chemicals may be estimated on an individual basis from their concentrations in blood or urine. The present document reviews sources of error in the collection, processing and storage of specimens for this biological monitoring. Physiological factors cause variation in the concentration of chemicals in the body fluids. Distribution of water depends on posture. Exercise and meals cause changes in blood constituents. The urine output varies and, thus, the concentrations of dissolved chemicals change. Many toxic chemicals show short half times in the blood; thus, their concentrations depend on the timing of the specimen collection. Skin absorption may result in dramatically different chemical concentrations in different parts of the circulation. The stability of chemicals in the collected specimens is generally limited: chemical deterioration, adsorption, precipitation, and evaporation are the main causes of losses. For many chemicals, especially for trace elements, contamination of the specimen is the overwhelmingly most important source of error. As the range of the chemicals measured is wide, the relative importance of the sources of error is different for different chemicals. Information on most chemicals is at present very limited. Thus, before commencing a program on biological exposure monitoring, it is advisable to search the optimal conditions for specimen collection, processing, and storage.