As a first step in the assessment of their possible bio-effects, coal-related materials were tested for mutagenicity in the Salmonella/microsome assay. Of three coal gasification by-products tested, only a tar was mutagenic for any of four Salmonella strains. The following liquefaction materials were mutagenic for strains TA1538, TA98, and/or TA100: A liquefaction vehicle oil and coal hydrogenation filtered liquid, separated bottoms, vacuum overhead, and vacuum bottoms. Neither powdered coal nor water produced as a by-product of the hydrogenation process was positive in the Salmonella test. No coal-related material was mutagenic for the missense mutant TA1535 or for any strain in the absence of metabolic activation provided by rat hepatic homogenates (S9). In all but one instance Aroclor 1254-induced S9 provided the maximum activation for mutagenesis. Fractionation of all samples was undertaken by serial extraction with organic solvents of increasing polarity (hexane, toluene, methylene chloride, acetonitrile). Highly mutagenic materials were found in fractions of the hydrogenation filtered liquid, vacuum overhead, and vacuum bottoms. Thus far non-mutagenic samples have not yielded mutagenic components upon fractionation.
The metabolism of DMBA by microsomes and various cell cultures has been widely studied. However, the biotransformation of this compound by intact organs has not been well characterized. In order to compare the metabolism of DMBA in the whole liver with that in subcellular preparations, we used an in situ single-pass rat liver perfusion system and rat liver microsomes. [14C]DMBA was infused into the livers of Sprague-Dawley rats during the first 60 min of a 120 min perfusion. HPLC analysis of extracts of perfusate samples indicated that DMBA was rapidly oxidized in this system to a series of metabolites. The major products were polar metabolites including the trans-5,6- and the trans-10,11-dihydrodiols (46%), the trans-3,4-dihydrodiol (5%) and the 7-OHM-12-MBA and the 12-OHM-7-MBA metabolites (12%) of DMBA. Microsomes prepared from livers of corn oil treated rats were incubated with [14C]DMBA for 60 min, then extracted. In the microsomal system the major DMBA metabolites were the trans-8,9-dihydrodiol (6%), the 7- and 12-hydroxymethyl (20%), and the 3- and 4-hydroxy (11%) of DMBA with the more polar metabolites and the trans-3,4-dihydrodiol present at lower levels (12 and 3% respectively). This is the first report of DMBA metabolism in a whole liver preparation and the results are clearly different from those obtained in subcellular preparations in our laboratory and in cell culture systems elsewhere. These results have important implications for understanding DMBA biotransformation in vivo.
In previous inhalation studies, rats exposed to aerosol concentrations of lead oxide (Pb2O3), 150 μg/m3; lead chloride (PbCl2), 100 μg/m3; nickel oxide (NiO), 120 μg/m3; and nickel chloride (NiCl2), 109 μg/m3; significant changes were observed in the lungs and alveolar macrophages. In this study the hydroiytic enzymes, acetylesterase, acid and alkaline phos-phatases, lysozyme, and beta-glucuronidase, in alveolar macrophages and lung washout fluid from rats subjected to the inhalation of the lead and nickel aerosols were examined. Washed alveolar macrophages from animals exposed to lead and nickel aerosols were found to contain reduced quantities of the various hydrolytic enzymes (except for acetylesterase) when compared with those from control rats. On the other hand, a significant increase in enzymatic activity was noted in lung washout fluid from exposed animals. The functional efficiency of macrophages, relative enzyme changes, and the mechanism of action of metals are discussed. It is important to note that the changes observed in these studies were from animals exposed to metallic concentrations near their Threshold Limit Values.
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