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Biomedical subjects

J R Allen

Publications and source records attributed to J R Allen.

At least 235 records · Page 13Linked to original sources

Responses of rats exposed to polychlorinated biphenyls for fifty-two weeks I. Comparison of tissue levels of PCB and biological changes.

Male Sprague-Dawley rats were fed a diet containing mixtures of polychlorinated biphenyls (PCB) isomers (Aroclor 1248, 1254 and 1262) at a concentration of 100 ppm in the diet for 52 weeks. During the subsequent 13 weeks the rats were placed on a control diet. Throughout the course of the experiment the animals ate well, were healthy in appearance and gained weight as rapidly as the control animals. Their hemograms were normal. In spite of the gross normalcy of these animals throughout the 52-week experimental period, clinical and morphologic examinations revealed distinct alterations. There was a decided increase in their total serum lipids and cholesterol and a transient increase in triglycerides accompanied by distinct morphological changes in the liver. Generalized liver hypertrophy and focal areas of hepatocellular degeneration were followed by a wide spectrum of repair processes. The tissue levels of PCB were greater in the animals receiving the higher chlorine mixtures. High levels persisted in these tissues even after the PCBs had been discontinued.

Adipose Tissue↗

Tissue distribution, binding properties and lesions produced by dehydroretronecine in the nonhuman primate.

Four-month-old rhesus monkeys were injected with 65 mg of [3H] dehydroretronecine per kg body weight and sacrificed at 6,12 and 24 h following injection. By the 24th h 13% of the dose had been eliminated in the urine. Although there were no feces, the extremely high radioactivity of the bile and intestinal contents suggested this route was a major one for the excretion of this compound. The 3H was distributed throughout the body by the 6th h with the greatest percentage being in the skin and muscle. However, per gram of tissue the gastric mucosa and bile showed the highest radioactivity. Likewise, it was in the gastric mucosa that the lesions produced by dehydroretronecine were the most severe. High levels of radioactivity persisted in the gastric mucosal lysates after washings with trichloroacetic acit (TCA) while only a small percentage of the (3)H remained in the washed liver lysate. It was determined that over 20% of the 3H was bound to mucosal protein and less than 1% to the nucleic acids.

Animals↗

Neoplastic transformation in tissues of rats exposed to monocrotaline or dehydroretronecine.

Male Sprague-Dawley rats received sc injections biweekly of either the pyrrolizidine alkaloid monocrotaline or its metabolite dehydroretronecine for 1 year. The animals were then observed for an additional 12 months for the induction of neoplasms. Of 60 rats that received dehydroretronecine, 39 developed rhabdomyosarcomas at the injection site, and 5 of these neoplasms metastasized. In the 60 monocrotaline-treated rats, 31 widely dispersed tumors of various cell types were recorded. The reason suggested for the variation in tissue response was that the metabolite dehydroretronecine is a proximate carcinogen, whereas monocrotaline must first be metabolized before its carcinogenic potential is realized.

Animals↗

In vitro generation of a chemically reactive metabolite of 2,5,2',5'-tetrachlorobiphenyl by rhesus monkey liver microsomes.

Incubation of tritiated 2,5,2',5'-tetrachlorobiphenyl with normal monkey liver microsomes in a NADPH-generating system results in the formation of active metabolite(s) of the [3H]2,5,2',5'-tetrachlorobiphenyl capable of covalently binding to Rna and protein isolated from the incubation mixture. The metabolite is not formed when the control microsomes are held at 100 degrees for 10 min prior to incubation. The addition of microsomal supernate to the solution causes an increase in the binding of the active metabolite to macromolecules while the addition of glutathione to the incubation medium significantly inhibits this increase.

Animals↗

Acquired resistance to ticks. I. Passive transfer of resistance.

Guinea-pigs developed resistance to larvae of the ixodid tick, Dermacentor andersoni, after one infestation. Resistance was characterized by guinea-pigs allowing fewer larvae to engorge (5-15%) during a second exposure than during an initial infestation (70-90%). Larvae feeding on resistant hosts weighed less than larvae engorging on a host with no previous exposure to ticks. Evidence is presented which indicates that this resistance can be passively transferred with viable lymph node cells, but not with serum, from resistant guinea-pigs. Recipients of cells from such resistant animals allowed significantly fewer larvae to engorge than did controls previously unexposed to ticks. This was not so in recipients of immune serum. The protection provided by passive transfer of cells from a resistant donor was not as complete as the protection afforded by natural exposure.

Animals↗

Acquired resistance to ticks. II. Effects of Cyclophosphamide on resistance.

Guinea-pig developed resistance to Dermacentor andersoni larvae after one infestation. Cyclophosphamide administered in one dose (300 mg/kg) 48 hr prior to an initial infestation with larvae blocked the acquisition of resistance. When cyclophosphamide was given in a similar regimen to guinea-pigs which had already acquired resistance, the expressin of resistance was partially blocked. It was proposed that the blockage of the acquisition of resistance further confirmed the immunological nature of tick resistance. Partial blockage of the expression of resistance by cyclophosphamide substantiated the presence of a humoral component to the resistance mechanism. The presence of a cell-mediated component was previously well established.

Animals↗

Biliary metabolites of 2,5,2',5'-tetrachlorobiphenyl in the rat.

Biliary metabolites of rats receiving 3H labeled 2,5,2',5'-tetrachlorobiphenyl, a component of commercial polychlorinated bipheyl (PCB) mixtures include 3-OH-2,5,2',5'-tetrachlorobiphenyl and a dihydrodiol tentatively identified as trans-3,4-dihydrodihydroxy-2,5,2',5'-tetrachlorobiphenyl. Metabolism of PCBs in the rat probably occurs in part through an arene oxide intermediate.

Animals↗

Disenecioyl dehydroretronecine--synthesis and acute hepatic toxicity of a pyrrolizidine alkaloid pyrrole analog.

Disenecioyl dehydroretronecine (DSDR), a semi-synthetic analog of the highly reactive pyrrole metabolites of the pyrrolizidine alkaloids, has been synthesized from disenecioyl retronecine. Rats which received 40 mg DSDR/kg body weight via the mesenteric vein showed multiple depressed areas (less than 2 mm in diameter) on the surface of the median lobe of the liver. Microscopically these areas consisted of hepatic venous occlusion, necrosis, and proliferation of fibroblasts and bile ducts in and around the portal triad. These hepatic lesions were similar to those produced by dehydroretrorcine.

Animals↗

Characterization of the DNA from the dinoflagellate Crypthecodinium cohnii and implications for nuclear organization.

Although dinoflagellates are eucaryotes, they possess many bacterial nuclear traits. For this reason they are thought by some to be evolutionary intermediates. Dinoflagellates also possess some unusual nuclear traits not seen in either bacteria or higher eucaryotes, such as a very large number of identical appearing, permanently condensed chromosomes suggesting polyteny or polyploidy. We have studied the DNA of the dinoflagellate Crypthecodinium cohnii with respect to DNA per cell, chromosome counts, and renaturation kinetics. The renaturation kinetic results tend to refute extreme polyteny and polyploidy as the mode of nuclear organization. This organism contains 55-60% repeated, interspersed DNA typical of higher eucaryotes. These results, along with the fact that dinoflagellate chromatin contains practically no basic protein, indicate that dinoflagellates may be organisms with a combination of both bacterial and eucaryotic traits.

Animals↗