Apoptosis in Daudi Human B Cells in Response to Benzo[a]pyrene and Benzo[a]pyrene-7,8-dihydrodiol

Salas, Virginia M.; Burchiel, Scott W.

doi:10.1006/taap.1998.8455

Cited by 83 publications

(48 citation statements)

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“…The observation that benzo[a]pyrenes alter signaling (71) and induce apoptosis (72) in vitro supports this concept. Abnormal cell death with release of normally sequestered antigens could theoretically contribute to autoimmunity.…”

Section: Signaling Modifiersmentioning

confidence: 65%

Environmentally induced autoimmune diseases: potential mechanisms.

Rao

Richardson

1999

Environ Health Perspect

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Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists.

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Section: Signaling Modifiersmentioning

confidence: 65%

Environmentally induced autoimmune diseases: potential mechanisms.

Rao

Richardson

1999

Environ Health Perspect

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“…The dominant formation of BaP-7,8-dihydrodiol under BaP-exposure is toxicologically of interest. This metabolite suppresses T-cell proliferation in mammals (Davila et al, 1996) and induces apoptosis in human B cells (Salas and Burchiel, 1998). Further metabolism of this compound may lead to BPDE, an intermediate of BaP that binds to DNA and had immunosuppressive effects in murine splenocytes (Kawabata and White, 1989).…”

Section: Discussionmentioning

confidence: 99%

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

et al. 2013

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Polycyclic aromatic hydrocarbons (PAHs) are immunotoxicants in fish. In mammals, phase I metabolites are believed to be critically involved in the immunotoxicity of PAHs. This mechanism has been suggested for fish as well. The present study investigates the capacity of immune organs (head kidney, spleen) of rainbow trout, Oncorhynchus mykiss, to metabolize the prototypic PAH, benzo [a]pyrene (BaP). To this end, we analyzed 1) the induction of enzymatic capacity measured as 7-ethoxyresorufin-O-deethylase (EROD) activity in immune organs compared with liver, 2) the organ profiles of BaP metabolites generated in vivo, and 3) rates of microsomal BaP metabolite production in vitro. All measurements were done for control fish and for fish treated with an intraperitoneal injection of 15 mg BaP/kg body weight. In exposed trout, the liver, head kidney, and spleen contained similar levels of BaP, whereas EROD induction differed significantly between the organs, with liver showing the highest induction factor (132.83), followed by head kidney (38.43) and spleen (1.43). Likewise, rates of microsomal metabolite formation experienced the highest induction in the liver of BaP-exposed trout, followed by the head kidney and spleen. Microsomes from control fish displayed tissue-specific differences in metabolite production. In contrast, in BaP-exposed trout, microsomes of all organs produced the potentially immunotoxic BaP-7,8-dihydrodiol as the main metabolite. The findings from this study show that PAHs, like BaP, are distributed into immune organs of fish and provide the first evidence that immune organs possess inducible PAH metabolism leading to in situ production of potentially immunotoxic PAH metabolites.

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“…Previous toxicity studies using laboratory animals indicate that the mammalian immune system is a sensitive target of persistent organic pollutants such as tetrachlorodibenzo-p-dioxin, PCBs, and PAHs (Tucker et al, 1986;Ladics et al, 1991;Stack et al, 1999). Many reports have documented the specific suppressive effects of the carcinogenic PAHs on both humoral and cell-mediated immunity in rodents and humans (Ladics et al, 1991;reviewed in White et al, 1994;Davila et al, 1996;Salas and Burchiel, 1998). Effects included decreased proliferation responses to Tcell mitogens as well as lymphoid cell death, lymphoid organ atrophy, altered lymphocyte subsets, apoptosis, decreased B-cell responses to mitogens and antigens, altered cytokine regulation, and changes in innate immune function.…”

Section: Discussionmentioning

confidence: 99%

Proliferative Responses of Harbor Seal (Phoca vitulina) T Lymphocytes to Model Marine Pollutants

Neale

Water²,

Harvey

et al. 2002

Journal of Immunology Research

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In recent years, population declines related to viral outbreaks in marine mammals have been associated with polluted coastal waters and high tissue concentrations of certain persistent, lipophilic contaminants. Such observations suggest a contributing role of contaminant-induced suppression of cell-mediated immunity leading to decreased host resistance. Here, we assessed the effects of the prototypic polycyclic aromatic hydrocarbon (PAH), benzo [a]pyrene (B[a]P), and two polychlorinated biphenyls (PCBs), CB-156 and CB-80, on the T-cell proliferative response to mitogen in harbor seal peripheral lymphocytes. Despite the variability associated with our samples from free-ranging harbor seals, we observed a clear suppressive effect of B[a]P (10 uM) exposure on T cell mitogenesis. Exposures to 10 uM CB-156 and CB-80, and 1.0 and 0.1 uM B[a]P, did not produce significant depression in lymphoproliferation. Exposure to the model PAH at 10 uM resulted in a 61% (range 34 -97%) average reduction in lymphoproliferation. We were able to rule out a direct cytotoxic effect of B[a]P, indicating that observed effects were due to altered T cell function. Based on our in vitro results, we hypothesize that extensive accumulation of PAH by top-trophic-level marine mammals could alter T cell activation in vivo and impaired cell-mediated immunity against viral pathogens.Keywords: Benzo[a]pyrene; Harbor seal; Immunotoxicity; Lymphoproliferation; PAH; PCB INTRODUCTIONUnderstanding immune alterations related to environmental contamination has become an important priority in marine mammal research because of the high incidence in recent years of mass mortality events, unexplained population declines, and strandings among marine mammal populations (Dietz et al., 1989; Marine Mammal Commission, 1999;Kennedy et al., 2000). These events have been largely attributed to disease outbreaks caused by established or newly identified members of the genus Morbillivirus (Geraci et al., 1982;Osterhaus and Vedder, 1988;Duignan et al., 1995). Common features of these massive die-offs include highly polluted habitat and high tissue concentrations in affected individuals of persistent, lipophilic contaminants, including those known to have deleterious effects on the immune systems of rodents and humans (Hall et al., 1992;Visser et al., 1993;Reijnders, 1994). Whereas contaminant-induced immune suppression has been suggested as a major contributing factor in marine mammal disease epizootics, causal relationships and potential mechanisms of immunotoxicity have not been established (Olsson et al., 1994; Marine Mammal Commission, 1999;van Loveren et al., 2000).The harbor seal (Phoca vitulina) is an ideal model organism for investigating contaminant-induced immune alterations in marine mammals. Fish-eating seals are longlived, maintain large adipose deposits, and occupy high trophic levels in the marine food chain, thus accumulating relatively high levels of lipophilic contaminants (Boon et al., 1987;Young et al., 1998; Neale, unpublished data). Among marine m...

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Apoptosis in Daudi Human B Cells in Response to Benzo[a]pyrene and Benzo[a]pyrene-7,8-dihydrodiol

Cited by 83 publications

References 41 publications

Environmentally induced autoimmune diseases: potential mechanisms.

Environmentally induced autoimmune diseases: potential mechanisms.

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

Proliferative Responses of Harbor Seal (Phoca vitulina) T Lymphocytes to Model Marine Pollutants

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