Assessment of myelotoxicity caused by environmental chemicals.

Boorman, Gary A.; Luster, Michael I.; Dean, Jack H.; Campbell, Martin L.

doi:10.1289/ehp.8243129

Cited by 35 publications

(9 citation statements)

References 37 publications

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“…This is not to say that LP assays are not a reliable predictor of immune alteration but, rather, may prove to be an extremely sensitive indicator of immunotoxicity, if appropriately interpreted. Support for this hypothesis has been provided in collaborative studies with Boorman (20). All data reported were obtained in animals administered dosage levels that did not induce overt signs of toxicity.…”

Section: Environmental Health Perspectivesmentioning

confidence: 89%

Cell-Mediated Immunity and Its Application in Toxicology

Luster¹,

Dean²,

Boorman³

1982

Environmental Health Perspectives

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JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) andBrogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives.A variety of in vivo and more recently in vitro assays have been described to assess cell mediated immunity (CMI). Two methods routinely employed in our laboratory to assess CMI following exposure to chemicals in rodents include delayed hypersensitivity and in vitro lymphoproliferation. Preliminary studies indicate that depressed delayed hypersensitivity responses, as performed by a radiometric assay, correlates with altered susceptibility to infectious agents and tumor cell challenge following exposure to immunotoxic chemicals. Furthermore, suppression of T-cell lymphoproliferative responses to at least 50% below control values correlated with depressed delayed hypersensitivity responses and altered host susceptibility. On the other hand, when suppression of T-cell lymphoproliferative responses are within 50% of control values, delayed hypersensitivity and host susceptibility parameters are not affected. Assuming adequate technical expertise and accurate data interpretation, CMI assays of these types can provide a valuable data base for toxicology studies and immunotoxicity assessment.This content downloaded from 91.

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Section: Environmental Health Perspectivesmentioning

confidence: 89%

Cell-Mediated Immunity and Its Application in Toxicology

Luster¹,

Dean²,

Boorman³

1982

Environmental Health Perspectives

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“…It has been shown that several cytotoxic substances are able to provoke a transient or permanent damage to hematopoietic stem cells, and as a consequence there is a significant impairment of the erythroid response capacity to a hemorrhagic insult [Trainor and Morley, 1976;Boorman et al, 1982]. The results presented here show that actually the contrary effect was produced, since not only in the intoxicated animals there was no impairment of the erythroid response to bleeding, but in fact there was a true activation of the erythropoietic system, as shown by the highly increased erythroid hypercellularity produced either in spleen or in bone marrow, which far exceeded that produced by bleeding in non-intoxicated animals.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, it has been shown that after recovery from the acute effects produced by several hematotoxins such as busulfan, ionizing radiations, etc., some degree of ''residual damage'' may persist, which is believed to be due to partial depletion of hematopoietic stem cells [Gong et al, 1969;Morley and Blake, 1974;Botnick et al, 1978]. [Boorman et al, 1982]. [Boorman et al, 1982].…”

Section: Introductionmentioning

confidence: 99%

Effects of multiple doses of T‐2 toxin on the erythroid response capacity of mice following an extensive experimental bleeding

Godoy¹,

Faifer²,

Velazco³

1997

Natural Toxins

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Total nucleated cellularity and total erythroid cell populations were measured in spleen and bone marrow of mice at different times after treatment with 3 daily doses of T-2 toxin (2.0 mg/kg). It was found that the initial depletion of hematopoietic cells produced by the toxin was rapidly reverted in spleen, giving way after 48 hr to a significant hypercellularity which after 10 days was 2.5 times the normal levels, but this effect was not observed in bone marrow, which slowly recovered normal cellularity after 5 days. The cytological analysis revealed that there was a highly significant shift in the ratio of erythroid to non-erythroid cells, since erythroid cell populations increased by about 8-fold in spleen and nearly 2-fold in bone marrow between 10 and 35 days after intoxication. In order to test the integrity of the hematopoietic reserve capacity, a hemorrhagic stress was produced in intoxicated animals at 10-50 days after toxin exposure. It was found that the erythroid response capacity was significantly higher in the intoxicated animals compared to anemic controls. The results suggest that the initial cytotoxic damage produced by T-2 toxin in the hematopoietic system is followed by a significant erythroid hypercellularity, which can confer an increased capacity for response to a hemorrhagic emergency. Nat. Toxins 5: 152-156, 1997. 1997

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“…Assays of colony formation of hematopoietic cells often detect exposure to contaminants before one can measure actual hematological changes (Luster et al, 1985;Schurig et al, 1985). Evidence has accumulated with laboratory animals that low-level exposure to certain mixtures of environmental chemicals can produce myelotoxicity in the absence of other manifestations of toxicity in parenchymal organs (Boorman et al, 1982). In particular, granulocyte-macrophage progenitor cells are often affected at lower levels of exposure to chemical mixtures than other hematopoietic cell lines (Hong et al, 1992).…”

Section: Evaluation Of Myelotoxicity In Cotton Rats (Sigmodon Hispidumentioning

confidence: 99%

Evaluation Of Myelotoxicity In Cotton Rats (Sigmodon hispidus) Exposed To Environmental Contaminants. I. In Vitro Bone-Marrow Progenitor Culture

Kim¹,

Stair²,

Lochmiller³

et al. 2001

Journal of Toxicology and Environmental Health, Part A

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Bone marrow is extremely sensitive to toxicants, and in vitro culture of bone-marrow progenitor cells has been shown to be a sensitive indicator of bone-marrow injury in laboratory rodents. The ability of a bone-marrow progenitor cell assay to detect myelotoxicity in a wild rodent model (cotton rat, Sigmodon hispidus) that inhabits many contaminated ecosystems in the southern United States was examined. Responsiveness of progenitor cells to recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and cotton rat lung-conditioned medium (LCM) was determined to optimize culture conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexamethasone (500 microg/kg) over a 5-d period. Administration of a high dose of cyclophosphamide caused nearly total suppression of colony formation of granulocyte-macrophage progenitor cells (CFU-GM). Marked histological changes in both the bone marrow and spleen were also observed in cotton rats treated with a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophosphamide- and dexamethasone-treated cotton rats was significantly suppressed compared to controls. The number of CFU-GM was consistently higher using LCM than recombinant murine GM-CSF. This reproducible, quantitative, in vitro bone-marrow progenitor cell culture system was a sensitive indicator of myelotoxicity in wild cotton rats and should be useful for monitoring chronic exposures to low levels of environmental toxicants in wild rodent populations.

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Assessment of myelotoxicity caused by environmental chemicals.

Cited by 35 publications

References 37 publications

Cell-Mediated Immunity and Its Application in Toxicology

Cell-Mediated Immunity and Its Application in Toxicology

Effects of multiple doses of T‐2 toxin on the erythroid response capacity of mice following an extensive experimental bleeding

Evaluation Of Myelotoxicity In Cotton Rats (Sigmodon hispidus) Exposed To Environmental Contaminants. I. In Vitro Bone-Marrow Progenitor Culture

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