Acute effects of benzene and cyclophosphamide exposure on cellular and humoral immunity of cotton rats,Sigmodon hispidus

McMurry, Scott T.; Lochmiller, Robert L.; Vestey, Michelle R.; Qualls, Charles W.; Elangbam, Chandikumar S.

doi:10.1007/bf01689741

Cited by 18 publications

(9 citation statements)

References 19 publications

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“…Relative immune organ weights and cellularity, circulating leukocytes, and indices of cell-mediated immunity (Con A-induced splenocyte proliferation, DTH responsiveness) were all negatively impacted by CY. These results parallel findings of a number of other rodent studies (Johnson et al 1982;Dean et al 1979;Bach and Strom 1985;McMurry et al 1991), and highlight the sensitivity of cotton rat immune function to xenobiotic contamination.…”

Section: Resultssupporting

confidence: 90%

“…A priori planned comparisons (single degree of freedom contrasts) were used in all Analysis of Variance procedures to compare means of major treatment components (benzene vs negative control, CY vs negative control, and 100 mg benzene vs 1,000 mg benzene). Previous studies of cotton rat immune function have demonstrated a great deal of variation in phenotypic expression of cellular and humoral immunity in adult and juvenile cotton rats (McMurry et aL 1991;Lochmiller et al 1993;Vestey et al 1993). Therefore, statistical differences between treatment and control groups were determined at the 10% level of significance.…”

Section: *Present Addressmentioning

confidence: 99%

“…Of all natural stressors, nutritional restriction ranks as one of the most important in determining overall condition and physiologic integrity of individuals within wildlife populations. Routine temporal and spatial variation in the nutritional quality of forage resources can influence behavior, reproduction, and survival in animal populations (White 1978;Flowerdew 1987).Immune response is one of several physiological markers of environmental contamination that has been extensively studied in laboratory rat and mouse models (Voss 1977) and more recently in wildlife species (Schrank et al 1990;McMurry et al 1991;Rocke and Samuel 1991). The immune system is an interactive and dynamic network of cells and soluble mediators which are sensitive to intrinsic and extrinsic stressors such as age, sex, reproductive condition, nutrition, and chemical stress (Lahita 1984;Dean et al 1986).…”

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confidence: 97%

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Cellular immune responses of nutritionally stressed juvenile cotton rats (Sigmodon hispidus) during acute benzene exposure

et al. 1994

Arch. Environ. Contam. Toxicol.

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Wild juvenile cotton rats (Sigmodon hispidus) were used in this study to examine the effects of exposure to cyclophosphamide (CY) or differing levels of benzene on selected measures of cellular immunity following dietary protein restriction. Benzene caused marginal immunotoxicity as indicated by suppressed splenocyte proliferation and total circulating neutrophils. Cyclophosphamide and also crude protein restriction induced severe immune lesions manifested as thymus and spleen atrophy, depressed delayed hypersensitivity response, reduced proliferative capacity of splenocytes, and reduced numbers of total leukocytes, lymphocytes, and splenocytes. Although severe immune modulation resulted from the individual effects of CY exposure and dietary protein restriction, there was little statistically significant toxicant-diet interaction.

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Section: Resultssupporting

confidence: 90%

Section: *Present Addressmentioning

confidence: 99%

mentioning

confidence: 97%

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Cellular immune responses of nutritionally stressed juvenile cotton rats (Sigmodon hispidus) during acute benzene exposure

et al. 1994

Arch. Environ. Contam. Toxicol.

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“…The majority of data available in literature about CBP and immunotoxicity was obtained from studies in animals [15,[25][26][27][28][29][30][31][32][33][34][35]. Data in humans are scarce and involves groups of workers during the exposure [36][37][38][39].…”

Section: Introductionmentioning

confidence: 98%

Phenotype analysis of lymphocytes of workers with chronic benzene poisoning

et al. 2005

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Lifetime exposure to benzene is associated to a variety of blood disorders, and except for the risk of cancer, almost nothing is known concerning health impairment in individuals who are no longer exposed. In Brazil, this exposure is one of the serious problems in workplaces, and many workers have been laid off their jobs due to this intoxication, particularly in the State of Bahia, the largest producer of benzene in Latin America, which is the area of this study. From a larger study to describe health effects and genetic polymorphisms among workers with chronic benzene poisoning (CBP), this previous specific investigation analyzes the association between CBP and the pattern of sub-populations of lymphocytes. The study was performed with a CBP group (n=24) and a control group with other occupational diseases (n=24); both were selected at the Workers Health Study Center in the State of Bahia, Brazil. Clinical and epidemiologic variables were collected from medical records and from a detailed questionnaire. The average age was similar in the two groups (51.1 and 50.7, respectively). Analyzing the mean proportions of the sub-populations of lymphocytes, statistically significant differences were found for T cytotoxic cells (TCD8) (27.9; 19.4; p=0.002) and T helper memory cell (CD4CD45RO) (31.2; 37.0; p=0.015), respectively, for the CBP group and control group. These results should be viewed with caution because of the small sample size, but they strengthen a previous impression that workers exposed to benzene have their immune system impaired, even in the long term, which may contribute to some disorders and carcinogenesis process. These workers must be strictly followed up in a medical surveillance program. Although this problem has been known for a long time, this is the first attempt to study these specific effects in Brazil.

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“…It also affects other lymphoid organs such as lymph nodes, spleen, and thymus. It has been reported that cyclophosphamide administered to cotton rats 3 d/wk at 50 mg/kg can induce immunosuppression (Johnson et al, 1982;McMurry et al, 1991McMurry et al, , 1994. Results are marked decreases in the number of lymphocytes in the thymus and spleen, the major targets for the cyclophosphamide action .…”

Section: Cfu-gm Assay In Cotton Rats 91mentioning

confidence: 94%

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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Acute effects of benzene and cyclophosphamide exposure on cellular and humoral immunity of cotton rats,Sigmodon hispidus

Cited by 18 publications

References 19 publications

Cellular immune responses of nutritionally stressed juvenile cotton rats (Sigmodon hispidus) during acute benzene exposure

Cellular immune responses of nutritionally stressed juvenile cotton rats (Sigmodon hispidus) during acute benzene exposure

Phenotype analysis of lymphocytes of workers with chronic benzene poisoning

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

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