Mechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis

doi:10.1016/0041-008X(92)90232-H

Toxicology and Applied Pharmacology

Volume 117, Issue 2, December 1992, Pages 155-164

https://doi.org/10.1016/0041-008X(92)90232-H Get rights and content

Abstract

The capacity for polycyclic aromatic hydrocarbons (PAH) to suppress immune cell function has been well documented. Nevertheless, mechanisms responsible for PAH immunosuppression and potential effects of PAH on lymphocyte development (lymphopoeisis) remain poorly defined. Murine bone marrow cultures were used in the present studies to determine if and by what mechanism(s) benzo[a]pyrene (B[a]P), a prototypic and highly carcinogenic PAH, suppresses B cell lymphopoiesis. Emphasis was placed on similarities between the processes leading to transformation and immunosuppression and on a possible role for programmed cell death (apoptosis) in B[a]P lymphotoxicity. Data presented herein indicate that: (1) B[a]P suppresses B cell lymphopoiesis in bone marrow cultures at extremely low concentrations (10⁻⁸ m); (2) benzo[e]pyrene, the relatively noncarcinogenic congener of B[a]P, is approximately 1000 times less potent than B[a]P in suppressing B cell lymphopoiesis; (3) bone marrow cells from PAH-resistant $DBA 2$ mice are less sensitive to B[a]P than cells from $C57BL 6$ mice; (4) B[a]P induces preB cell apoptosis; and (5) α-naphthaflavone, an inhibitor of Ahreceptor dependent, P450 isoenzyme activity, blocks B[a]P-mediated preB cell apoptosis and inhibits B[a]P-dependent suppression of lymphopoiesis. The results support the hypothesis that B[a]P suppression of B cell lymphopoiesis is mediated at least in part by the induction of programmed cell death and that the Ah receptor and/or P450 isoenzymes are involved in this process. The results suggest the potential for PAH to affect development of the B lymphocyte repertoire.

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Regular articleMechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis

Abstract

Immunol. Today

Biochem. Pharmacol.

Int. J. Immunopharmacol.

Immunopharmacology

Toxicol. Appl. Pharmacol.

Toxicology

Immunopharmacology

Toxicol. Appl. Pharmacol.

Environ. Res.

Toxicol. Appl. Pharmacol.

Toxicol. Appl. Pharmacol.

Int. J. Immunopharmacol.

Arch. Biochem. Biophys.

Adv. Genet.

J. Immunol. Methods

J. Biol. Chem.

Toxicol. Appl. Pharmacol.

Immunopharmacology

J. Immunol. Methods

Anti-immunoglobulins induce death by apoptosis in WEHI-231 B lymphoma cells

Eur. J. Immunol.

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Mol. Pharmacol.

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Environ. Health Perspect.

Purification and N-terminal amino acid sequence of the Ah receptor from C57BL6J mouse

Molec. Pharmacol.

Xenobiotic metabolism and mutation in a human lymphoblastoid cell line

Chem. Biol. Interact.

Immune suppression following exposure of mice to the carcinogen benzo(a)pyrene but not the noncarcinogenic benzo(e)pyrene

Clin. Exp. Immunol.

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J. Immunol.

Regular article
Mechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis

Purification and N-terminal amino acid sequence of the Ah receptor from $C57BL 6J$ mouse