P A Talcott

University of Idaho, Moscow, ID, United States

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Publications (16)20.9 Total impact

  • Patricia A. Talcott, Loren D. Koller
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    ABSTRACT: Approximately 200 female Swiss-Webster mice, six to eight weeks of age, were divided into eight groups. Three of these groups were fed 10, 100, or 250 ppm Aroclor 1254. One group was treated with 1000 ppm lead. Three groups were exposed simultaneously to lead and Aroclor 1254 at concentrations of 10 ppm PCB + 1000 ppm Pb, 100 ppm PCB + 1000 ppm Pb, and 250 ppm PCB + 1000 ppm Pb. Control mice received deionized water and rat food only. All groups were exposed for a period of 12 wk, then bred, with exposure continued throughout gestation and lactation. Offspring were weaned onto the control diet at 3 wk of age. Results from this study indicate a varied effect of lead and/or PCBs on body and organ weights of both dams and their pups, no noticeable detrimental effect on reproduction, and very little effect on the pups' ability to mount an immune response upon challenge with foreign antigens.
    Journal of Toxicology and Environmental Health 10/2009; 12(2-3):337-52. · 1.81 Impact Factor
  • G G Mather, P A Talcott, J H Exon
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    ABSTRACT: A tumor model in the Sprague-Dawley rat has been developed and characterized in our laboratory using the polycyclic aromatic hydrocarbon 3-methylcholanthrene (3MC). Interactions between the tumorigenic process and the natural killer cell (NK) response were investigated in this study. Rats given a single injection of 1.5 mg 3MC had reduced NK activity the first three weeks after injection when compared to vehicle treated controls. Tumor incidence in this group reached 45% and 76% 12 and 20 weeks, respectively, after the 3MC injection. Cell lines were established from six of these tumors and were tested for in vitro lysis by NK cells. Sensitivity of these cells ranged from 2.9 to 12.2% compared to 32.3 to 37.5% for the NK sensitive YAC-1 target cells. Rabbit antiasialo GM-1 antibody (ASGM-1) was used to effect in vivo reductions of NK function at arbitrarily selected times after 3MC injection. Tumor incidence in the group of rats treated to reduce NK activity at the time of initiation (0-2 weeks) reached 100% in 20 weeks compared to 67% in the companion 3MC treated controls. The number of days to tumor was also decreased from 93 to 77 days in this group. Rats treated to reduce NK activity at other times (5-7 weeks or 10-12 weeks) did not have alterations in tumor incidence or latency that were different from controls. The study supports a role for NK cells in the early detection and removal of transformed cells and points out the dangers of transient immunosuppression.
    Immunobiology 07/1994; 190(4-5):333-45. · 2.81 Impact Factor
  • P A Talcott, G G Mather, E H Kowitz
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    ABSTRACT: A diagnosis of cholecalciferol toxicity in a young dog was made on the basis of adequate history and the finding of extremely elevated serum calcium levels. The traditional treatment of fluid therapy, diuresis and corticosteroids resulted in lowering the serum calcium levels over a 5-d period. The dog displayed clinical signs of severe depression, anorexia and intermittent vomiting during this time interval. Serum calcium levels rose on day 6 and remained elevated up until the dog was euthanized on day 9. Gross and histopathological examinations revealed diffuse metastatic mineralization throughout the body, particularly involving the lung, kidney, atria and stomach. The amount of cholecalciferol ingested was determined well below the lethal dose reported in dogs. This report indicates that young dogs may be much more susceptible to the lethal effects of this compound than initially believed.
    Veterinary and human toxicology 07/1991; 33(3):252-6.
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    ABSTRACT: Male Sprague-Dawley rats were exposed to either 2000 or 6000 ppm of 2-methoxyethanol (ME) or 2-butoxyethanol (BE) and females were exposed to either 1600 or 4800 ppm of these compounds in the drinking water for 21 days. Body weights were decreased in male rats exposed to the high doses of both chemicals, while body weights of females exposed to either dose of BE were decreased. Male and female rats exposed to either concentration of ME had a dose-related reduction in thymus weights. Testis weight was significantly lower in male rats exposed to the high dose of ME. Dose-related increases in natural killer (NK) cell cytotoxic activities and decreases in specific antibody production were observed in all rats treated with ME. Rats exposed to the low dose of BE also had enhanced NK cell activity. Splenocyte production of interferon-γ was decreased in male rats exposed to either dose of ME and in females treated with the high dose of ME. Spleen cell numbers were reduced in males exposed to the high dose of ME and females given either dose of ME. It appears that the immune system is a sensitive target of ME but not BE. The effects of ME on immune function differ depending on the immune parameter assessed. Enhanced NK cell activity may partially explain the observations of others that certain glycol ethers have antitumor effects in vivo.
    Fundamental and Applied Toxicology 06/1991;
  • P A Talcott, J H Exon, L D Koller
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    ABSTRACT: Eight-week-old male Sprague-Dawley rats were exposed to the carcinogen methylnitrosourea (MNU) via gastric intubation at doses of either 10 or 20 mg/kg body wt. Rats were treated once a week for 4 weeks, then once every 2 weeks for 1 month, for a total of 6 treatments. MNU was found to exert no consistent significant immunosuppressive effects in vivo as measured by spleen natural killer (NK) cell cytotoxicity, interleukin-2 (IL-2) production by splenic lymphocytes and prostaglandin E2 (PGE2) production by adherent peritoneal macrophages. In contrast, splenic NK cell cytotoxicity and IL-2 production of MNU-treated rats were actually elevated at several of the later sampling periods. PGE2 production was also elevated in MNU-treated rats in the later sampling periods. Body weights of MNU-treated rats were markedly decreased as early as 4 weeks following the initial MNU treatment. This suppression persisted throughout the study. The most dramatic change in organ weights was seen in the thymus. Thymus weights of all MNU-treated rats were significantly decreased 1 day after treatment and persisted for 4 weeks. By the 60 day sampling period, thymus weights were not significantly different from controls. However, by 120 and 180 days, thymus weights again were significantly lowered in those rats receiving MNU. These changes in thymus weights were accompanied histologically by initial cortical thinning and progressive loss of cortical thymocytes followed by the appearance of hyperplastic and neoplastic cells. It thus appears that the carcinogenic effect of MNU is not related to a depression of the immune surveillance system, at least as measured by NK cell activity.
    Carcinogenesis 06/1990; 11(5):829-34. · 5.64 Impact Factor
  • P A Talcott, J H Exon, G G Mather, L D Koller
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    ABSTRACT: The carcinogen 3-methylcholanthrene (3-MC) was found to exert immunosuppressive effects both in vitro and in vivo in this study. Spleen cells from 8-week-old male, Sprague-Dawley (S-D) rats exposed to 1, 10 or 100 micrograms/ml 3-MC in vitro for 18 h exhibited a dose-dependent decrease in natural killer (NK) cell cytotoxicity against the YAC-1 tumor target cells in a 4 h 51Cr-release assay. Peritoneal macrophage production of prostaglandin E2 (PGE2) was significantly decreased at all three 3-MC concentrations following a 24 h exposure in vitro. No effect of 3-MC on splenic interleukin-2 (IL-2) production was observed. A separate group of rats was inoculated with a single subcutaneous dose of 5 or 10 mg 3-MC and cytotoxic activity of spleen NK cells was examined at 1, 2, 3, 7, 14, 21, 28, 60, 120 and 180 days after the 3-MC injection. Natural killer cell cytotoxicity was suppressed as early as 24 h after 3-MC injection and persisted up to 21 days. This decrease in NK activity was accompanied by a decreased production of splenic interferon and elevated production of PGE2 by peritoneal macrophages. Natural killer cell cytotoxicity was elevated in the 3-MC-treated rats at 28 and 60 days post-treatment. At 120 and 180 days post-3-MC treatment, when the rats were bearing palpable chemically-induced tumors, NK activity was again significantly depressed. In addition, 3-MC-induced tumors were surgically removed and cultured in vitro. Supernatants from these tumor cell lines were shown to markedly inhibit NK cytotoxicity when tested in vitro. Preliminary results indicate that this inhibition may be mediated by prostaglandins.
    International Journal of Immunopharmacology 02/1990; 12(8):917-26.
  • P TALCOTT, J EXON, G MATHER, L KOLLER
    International Journal of Immunopharmacology - INT J IMMUNOPHARMACOL. 01/1990; 12(8):917-926.
  • Jerry H. Exon, Nancy I. Kerkvliet, Patricia A. Talcott
    Journal of Environmental Science and Health Part C-environmental Carcinogenesis & Ecotoxicology Reviews - J ENVIRON SCI HEALTH C-ENVIR. 01/1987; 5(1):73-120.
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    ABSTRACT: A model for assessing immunotoxicologic effects of chemicals and drugs was developed in the Sprague-Dawley rat whereby multiple concomitant immunoassays were performed in a single animal. The multiple parameters of immunity assessed in each rat included T cell-dependent IgG antibody production, delayed hypersensitivity, natural killer cell cytotoxicity, and production of three potent immune regulating immunocytokines: macrophage-derived interleukin 1 and prostaglandin E2, and lymphocyte-derived interleukin 2. Splenocyte and resident peritoneal macrophage numbers were also quantitated and spleen and thymus weights recorded. The sensitivity of this animal model was tested by treating rats with the immune-potentiating drugs, NPT 15392 (erythro-9-[2-hydroxy,3-nonyl]hypoxanthine) and avridine (N,N-dioctadecyl-N',N'-bis-[2-hydroxyethyl]propanediamine, or the immune-suppressive drugs, cyclophosphamide (N,N-bis[2-chloroethyl]tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine -2-oxide) and dexamethasone. Rats treated with NPT 15392 or avridine generally had enhanced immune responses, while those treated with cyclophosphamide or dexamethasone had decreased immune responses. Differential responsiveness of various immunocyte populations within individual rats to different drugs, or to doses of the same drug, indicates the efficacy of measuring multiple responses within the same animal. The multiassay-single animal approach represents an economical, versatile, sensitive, and relatively comprehensive paradigm for assessing immunotoxicologic/pharmacologic properties of chemicals and drugs. The approach is extremely economical since multiple immune responses are evaluated in each animal. The approach is versatile because it is amenable to incorporation of a variety of in vitro and in vivo assays and could be applied to almost any species. The model is relatively comprehensive because major types of immune responses/immunocyte populations and immunoregulatory pathways are tested. Finally, the model is sensitive for detecting immunosuppression as well as immunoenhancement, as validated by the use of known immune response modifiers in this study.
    Fundamental and Applied Toxicology 10/1986; 7(3):387-97.
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    ABSTRACT: It is generally accepted that Selenium (Se) is necessary for optimum performance of the immune system. Selenium deficiency results in immune suppression but little is known concerning the effect of excess Se on immune function. Recent evidence suggests that oral Se supplementation may impede oncogenesis, but the mechanism of this action is currently unknown. Conversely, under certain conditions, Se is suspected of promoting neoplasia. The studies described herein delineate the effects of excess Se (0.5, 2.0 or 5.0 p.p.m.) on specific immune functions of Se-adequate rats, namely, antibody synthesis, delayed-type hypersensitivity (DTH), natural killer (NK) cell activity, prostaglandin E2 (PGE2) synthesis, and interleukin 1 (IL-1) activity. Selenium administered to female Sprague-Dawley rats for 10 weeks at 0.5 and 2.0 p.p.m. resulted in significant (P less than or equal to 0.01) enhancement of splenic NK activity while the NK response in the 5.0 p.p.m. Se-treated rats was equivalent to the non-Se-treated controls. Conversely, the DTH response was significantly (P less than or equal to 0.01) suppressed at all three dosages while antibody synthesis and prostaglandin E2 activity were significantly (P less than or equal to 0.05) reduced compared to the controls at the highest dosage of Se. IL-1 activity was unaffected by Se exposure. These data could partially explain the contradictory oncogenic characteristics of Se. For instance, tumours that are NK sensitive could be prevented and/or responsive to Se therapy, while NK insensitive neoplasms could be enhanced by Se supplementation due to the impaired function of both humoral and cell-mediated immunity.
    Clinical & Experimental Immunology 04/1986; 63(3):570-6. · 3.41 Impact Factor
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    ABSTRACT: Tumor growth and regression was studied in C57BL/6J mice injected with Moloney sarcoma virus (MSV) and treated with the interferon (IFN)-inducing drug, avridine. Avridine decreased the persistence of tumors when given one or five days after virus, but shortened the prepatent period and increased persistence if given one day prior to virus. Additional studies were undertaken to study the role that serum interferon and natural killer (NK) cell activity might have in this phenomenon. Interferon levels were greatly enhanced (over that induced by virus alone or avridine alone) when avridine was given one day after, but not one day before, virus. Six days after viral infection, interferon titers had returned to near zero but could be boosted by injecting avridine at day 5. Multiple injections of avridine before and after virus resulted in refractoriness to interferon induction and tumor persistence. NK activity was greatly increased by virus at two days post-infection, and avridine given one day after infection significantly enhanced cytotoxicity of these splenic cells against tumor cells. By six days after infection, NK activity had returned to normal but could be increased by avridine given at five days post-infection. It appeared that high levels of interferon induced by avridine given at one or five days after infection increased NK activity and may have been responsible for enhanced regression. Pre-treatment by avridine had little effect on interferon levels over that induced by virus alone, but that did not explain the enhancement of tumor growth since NK activity was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
    International Journal of Immunopharmacology 02/1986; 8(6):553-9.
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    ABSTRACT: Multiple concomitant immune responses were assessed in individual rats following treatment with the immunoenhancing drugs, isoprinosine (5 or 50 mg/kg), NPT 15392 (0.1 or 1.0 mg/kg) and avridine (1 or 25 mg/kg), or the immunosuppressant, cyclophosphamide (75 mg/kg). Immune responses assessed in each rat were specific antibody synthesis, delayed-type hypersensitivity (DTH), natural killer cell (NKC) cytotoxicity and production of three immunoregulatory cytokines, interleukin 1 (IL1), interleukin 2 (IL2) and prostaglandin E2 (PGE2). Spleen and thymus weights and numbers of splenocytes and resident peritoneal cells were also recorded. Rats treated with isoprinosine had dose-related, significant increases in spleen weights and DTH reactions. Rats treated with NPT 15392 had significantly enhanced DTH reactions at the 0.1 mg/kg dose. Rats treated with the 25 mg/kg dose of avridine had significantly increased spleen weights, DTH reactions and NKC cytotoxicity. The effect of avridine treatment on DTH reactions and IL1 and IL2 production was inverse to the dose administered, while the NKC response was directly related to the dose. Thymus weights, antibody production and PGE2 synthesis were not significantly altered in rats treated with isoprinosine, NPT 15392 or avridine. Cyclophosphamide-treated rats had significantly reduced spleen and thymus weights, antibody synthesis, DTH reactions, NKC cytotoxicity and IL2 production, but IL1 and PGE2 synthesis were significantly elevated. It can be concluded that isoprinosine, NPT 15392 and avridine act as general immunostimulants in the rat, with avridine having the greatest effect under these experimental conditions. It also appears that these drugs are differentially immunoselective in the rat and this effect is at least partially related to the dose administered. These results could be of significance in the selective therapeutic manipulation of different arms of the immune system. Also, enhanced production of PGE2 following cyclophosphamide treatment may contribute to the immunosuppressive effects of this drug.
    International Journal of Immunopharmacology 02/1986; 8(1):53-62.
  • J H Exon, P A Talcott, L D Koller
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    ABSTRACT: Interleukin 2 (IL2) activity, natural killer cell (NKC) cytotoxicity, and serum antibody (Ab) levels were assessed in rats exposed to 10 or 1000 ppm lead (Pb) as lead acetate in the drinking water or 50 or 500 ppm polychlorinated biphenyls (PCB) as Aroclor 1254 in the feed for 10 weeks or injected one time with 75 mg/kg cyclophosphamide (CY). Assays for IL2 activity and NKC cytotoxicity were also performed following in vitro exposure of rat splenocytes to Pb (0.4 or 40 micrograms/ml) or PCB (0.4 or 20.0 micrograms/ml) for 24 hr in vitro. NKC cytotoxicity and IL2 activity were significantly suppressed following in vitro exposure to either Pb or PCB. Chronic exposure to PCB, but not Pb, significantly reduced NKC cytolytic activity and significantly elevated Con A-stimulated IL2 activity. Ab synthesis was significantly suppressed in groups of rats chronically exposed to Pb or PCB. CY-injected rats had significantly reduced IL2 activity, NKC cytotoxicity, and Ab levels. High background levels of IL2, presumably induced by KLH injections shortly before termination, were significantly suppressed in PCB-, Pb-, and CY-treated rats. This suppression of IL2 activity was completely reversed by in vitro stimulation with Con A in Pb- or PCB-, but not CY-, treated groups. These results indicate that PCB, Pb, and CY alter IL2 synthesis and adversely affect NKC cytotoxicity and Ab synthesis following in vivo or in vitro exposure. The effects of PCB on NKC cytotoxicity may partially explain the tumor-promoting effect of this chemical via compromising immunosurveillance.
    Fundamental and Applied Toxicology 03/1985; 5(1):158-64.
  • Patricia A. Talcott, Loren D. Koller, Jerry H. Exon
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    ABSTRACT: Splenic natural killer (NK) cell cytotoxicity was assessed in rats chronically exposed to lead (Pb) as lead acetate in the drinking water or polychlorinated biphenyl (PCB) as Aroclor 1254 in the feed. Rats treated with cyclophosphamide were included as positive immunosuppressed controls. Weanling, male Sprague-Dawley rats exposed to 50 and 500 ppm PCB in the feed for ten weeks exhibited significantly suppressed (P less than 0.01) splenic NK activity. Cyclophosphamide injected i.p. six days prior to termination at a dose of 75 mg/kg also significantly inhibited splenic NK activity. NK cell activity was reduced, though not significantly, in spleen cells isolated from animals exposed to 10 and 1000 ppm Pb as Pb acetate in the drinking water for ten weeks. In vitro exposure of rat spleen cells to PCB at concentrations of 0.4 and 20.0 micrograms/ml similarly resulted in a significant depression of splenic NK cell activity. In addition, in vitro exposure to lead at the same concentrations resulted in suppressed NK cell cytotoxicity of rat splenocytes. These results indicate that two environmental contaminants have the ability to adversely affect NK cell cytotoxicity. The effects seen here with Pb and PCB on NK cells may in part explain the tumor inducing effect these chemicals are suspected of possessing via compromising the immune surveillance system.
    International Journal of Immunopharmacology 02/1985; 7(2):255-61.
  • P A Talcott, J H Exon, L D Koller
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    ABSTRACT: Weanling, female Sprague--Dawley rats were divided into 14 separate groups. Three of these groups were administered 0.5, 2.0 or 5.0 ppm selenium (Se) in the drinking water for 10 weeks. Three groups received intraperitoneal injections of 1, 5 or 10 mg/kg diethylnitrosamine (DEN) twice weekly for 10 weeks. The remaining animals received 0.150% or 0.316% ethylurea (EU) in the feed and 1 or 10 ppm nitrite as sodium nitrite in the drinking water either alone or in combination. Separate groups of rats treated with cyclophosphamide (CY) were included as positive immuno-suppressed controls. Following the 10-week chemical exposure period, splenic natural killer (NK) cell-mediated cytotoxicity was assessed by a 4-h chromium release assay using YAC-1 tumor cells as targets. The NK cell cytotoxic response was enhanced in both the low and medium dose selenium-exposed groups. In contrast, rats exposed to 0.316% EU + 10 ppm NO2 had significantly depressed NK cell activity. CY treatment also resulted in a significant reduction of splenic NK cell cytotoxicity.
    Cancer Letters 08/1984; 23(3):313-22. · 5.02 Impact Factor
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    ABSTRACT: Many drugs and other chemicals can alter cell-mediated immunity (CMI), a response that often correlates with delayed-type hypersensitivity (DTH). Several DTH assays were evaluated to determine a method best suited for assessing chemically induced modulation of CMI in rats. The effects of various antigens, adjuvants, doses, routes, and immunosuppressants were investigated. The DTH method which produced optimum results in rats uses a footpad swelling reaction elicited by specific preparations of bovine serum albumin (BSA) and Freund's complete adjuvant (FCA). The rats were sensitized with 100 μg BSA in FCA injected subcutaneously at the base of the tail, and were challenged 7 days later with 75 μl of 2% heat-aggregated BSA suspension injected into the left rear footpad. Footpad swelling was measured with pressure calipers 24 h later and compared to the contralateral footpad which was sham-injected with 75 μl of physiological saline. Antigen-injected footpads were nearly double the thickness (7–8 mm) of the control footpads (3–4 mm), and variation between animals was small (CV = 5%). Dexamethasone and cyclophosphamide significantly suppressed the DTH reaction. Histopathological examination of the DTH reaction sites revealed a mononuclear cell infiltrate which is characteristic of type IV hypersensitivity. In addition to being highly quantitative and sensitive, this method provides a simple and reproducible assessment of CMI responses in the rat.
    Journal of Immunological Methods 06/1984; · 2.23 Impact Factor