Pulmonary O-methyl transferases.
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Animals↗
Biomedical subjects
F C Law
Publications and source records attributed to F C Law.
Effects of nitrogen dioxide and 3-methylcholanthrene on pulmonary enzymes.
Guinea pig lung phenol-O-methyltransferase, catechol-O-methyltransferase, and benzpyrene hydroxylase activities were examined after nitrogen dioxide and 3-methylcholanthrene treatment. While benzypyrene hydroxylase activity was enhanced by 3-methylcholanthrene, none of the pulmonary enzyme activities was altered after exposure to either 40 or 70 ppm of nitrogen dioxide for 2 hr.
Benzopyrene Hydroxylase↗
Distribution of benzo[a]pyrene in pregnant rats following inhalation exposure and a comparison with similar data obtained with pyrene.
Eight pregnant rats were exposed, on the 17th day of gestation, for 95 min to a microcondensation aerosol of benzo[a]pyrene at five different atmospheric concentrations between 200 and 800 mg m-3 in a 'head-only' inhalation chamber. Five rats were killed immediately following the exposure and three were killed at 6 h post-dosing. Concentrations of the radiolabel and 'free' benzo[a]pyrene were measured in the individual fetuses and in the maternal blood, fat, kidney, liver and lung. Distribution to the fetus did not appear to be related to its position on the uterine horn and the uptake of benzo[a]pyrene was non-linear with increasing exposure concentrations, which was similar to the observations previously reported for pyrene. The levels of benzo[a]pyrene were much higher in the fetus and, especially, the lung than those observed in the pyrene study; so also were the levels of total metabolites in these tissues, which might, in part, account for the carcinogenic potency of benzo[a] pyrene.
Administration, Inhalation↗
The dispositional kinetics of phencyclidine and its N-ethylamine analogue in rats.
The uptake kinetics of [3H]-labelled phencyclidine (PCP) and N-ethyl-l-phenycyclohexylamine (PCE) in rats, measured in terms of decreases in the blood concentrations of the drugs after i.v. administration of a single 1.09 mumol dose, were not significantly different. Within a week of administration, the rats excreted about 93% of the [3H]-PCP and about 65% of [3H]-PCE via their urine and faeces; their urine contained nore [3H], mainly as metabolites of [3H]-PCP and of [3H]-PCE, than their faeces. Similarly, more [3H] remained in the tissues of rats treated with [3H]-PCE than in the tissues of [3H4-PCP-treated rats. The fact that PCE is metabolized and excreted more slowly than PCP may account for the higher psychotropic effects of PCE.
Animals↗
Neoplastic transformation of cells by soluble but not particulate forms of metals used in orthopaedic implants.
Recent developments in cell culture techniques have made it possible to study the cellular mechanisms involved in carcinogenesis and to apply these methods as screening tools in vitro. This study investigated and compared the ability of the metals most commonly used in orthopedic implants to induce toxicity and neoplastic transformation in the C3H10T1/2 mouse fibroblast cell line. Eight metals (cobalt, chromium, nickel, iron, molybdenum, aluminium, vanadium and titanium) and their alloys (stainless steel, cobalt-chrome alloy and titanium alloy) were tested, both as soluble salts and as solid particles. There were marked differences between the various metals in terms of both toxicity and transforming ability. Significant increases in the incidence of cell transformation were seen with soluble forms of cobalt, chromium, nickel and molybdenum but not with iron, aluminium, vanadium or titanium. For most of the metals. transforming ability was directly related to toxicity, although this correlation did not hold for either molybdenum or vanadium. The physical form of the metal was critically important in determining its effects, and transformation occurred only with soluble metal salts.
Alloys↗
Binding of 14C-furazolidone metabolites to the muscular and hepatic proteins of trout.
A high level of 14C was found to bind irreversibly with the liver proteins of rainbow trout (Oncorhyncus mykiss) exposed to 135 mg/kg bodyweight of 14C-labelled furazolidone (14C-FZ) in fish feed daily for 10 days. After the cessation of 14C-FZ treatment, hepatic protein-bound 14C in trout stayed high for at least 30 days. The chemical identity of protein-bound 14C remained to be elucidated. However, a part of the protein-bound 14C in the liver and muscle could be released as 3-amino-2-oxazolidinone by acid hydrolysis. The formation of protein-bound 14C in the liver was investigated further with trout dosed intravenously with different 14C-FZ doses at 10 degrees C or with 5 mg/kg FZ at different water temperatures. 14C binding to the liver proteins was found to increase with increasing FZ dose or water temperature. Results of these studies indicate that protein-bound 14C in the muscle and liver of trout is related to the formation of reactive intermediates from FZ. However, additional studies on the identities of the protein-bound FZ residues are required before they can serve as useful biomarkers to monitor FZ exposure in farm fish.
Administration, Oral↗
The perinatal development of epoxide-metabolizing enzyme activities in liver and extrahepatic organs of guinea pig and rabbit.
We have measured the activities of epoxide hydrase in microsomes and glutathione S-epoxidetransferase and glutathione S-aryltransferase in cytosol fractions of liver, lungs, kidneys, and small intestine from fetal and neonatal guinea pigs and rabbits. The rates at which adult values of these enzyme activities are reached in extrahepatic tissues differ from the rates of maturation of the hepatic enzyme activities for both species. In addition, the two pathways of epoxide metabolism studied here developed with age at different rates in any one organ. However, both cytosol glutathione S-transferases showed very similar developmental profiles in any one organ. It was especially interesting that the activities of both glutathione S-transferases were within the adult range in pulmonary cytosol fraction of guinea pig and rabbit before birth. Intestinal microsomes did not have adult values for epoxide hydrase activity until several weeks after birth. A feature common to both epoxide-metabolizing activities in hepatic and extrahepatic organs was a drop in mean specific activity, sometimes not statistically significant, around the time of birth. This decrease appeared to be due to dilution of the active enzyme with other protein, inasmuch as the total organ activity, in general, showed no such decline. We found that the pattern of development of hepatic microsomal epoxide hydrase activity was similar to developmental patterns published by others for hepatic microsomal mixed-function oxidases, and also that development of hepatic cytosol glutathione S-transferase was similar to hepatic development of glutathione S-transferase towards other substrates described in the literature.
Aging↗
Metabolism and disposition of alpha1-tetrahydrocannabinol by the isolated perfused rabbit lung.
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Animals↗
Studies on the pharmacokinetics and metabolism of 4-chlorodiphenyl ether in rats.
The metabolic disposition of 14C-labeled 4-chlorodiphenyl ether ([14C]4-CDE) was examined in rats following iv administration of a single dose (850 nmol/kg). [14C]4-CDE decayed rapidly from the blood since no unchanged [14C]4-CDE was detected in the blood beyond 2 hr after [14C]4-CDE administration. The dispositional kinetics of [14C]4-CDE in rats were best described by a two-compartment open pharmacokinetic model. Total radioactivity was excreted slowly from rats; about 41% and 33% of the administered dose were excreted into the urine and feces, respectively, within 1 week after chemical administration. About 5% of the total radioactivity administered to rats was excreted into the bile in 1 hr. The bulk of the radioactivity in the excreta was due to the presence of [14C]4-CDE metabolites. 14C-labeled 4'-hydroxy-4-CDE was the major metabolite and accounted for at least 90% of the radioactivity in the urine. The metabolic conversion of [14C]4-CDE to 14C-labeled 4'-hydroxy-4-CDE was corroborated by in vitro studies with liver microsomes of rats. In addition, [14C]4-CDE was converted by liver microsomes to reactive metabolites which bound irreversibly to microsomal protein. An arene oxide is suggested as the intermediate metabolite in the biotransformation of [14C]4-CDE by rats.
Animals↗
Metabolism of xenobiotics by the isolated perfused lung. Comparison with in vitro incubations.
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Animals↗
Rates of phencyclidine metabolism by the isolated perfused lung, lung microsomes, and liver microsomes of rabbits.
The metabolism of phencyclidine (PCP) was examined in the isolated perfused lung (lPL), lung microsomes, and liver microsomes of rabbits. The concentration of PCP in the IPL perfusate decreased rapidly with concomitant increases in the concentrations of PCP metabolites. The total rate of PCP metabolite appearance in the perfusate of the IPL was 77.4 nmol/lung/min. The apparent Vmax of PCP metabolism by the lung and liver microsomes were 1.52 and 22.9 nmol of PCP metabolised per mg of microsomal protein per min, respectively. Extrapolated to the whole lung, the apparent Vmax of PCP metabolism by lung microsomes was equivalent to 78.6 nmol of PCP metabolized per lung per min, essentially the same as that for the IPL.
Animals↗