This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kawabata, T. T. Articles by White, K. L. Search for Related Content PubMed PubMed Citation Articles by Kawabata, T. T. Articles by White, K. L., Jr.

Suppression of the in Vitro Humoral Immune Response of Mouse Splenocytes by Benzo(a)pyrene Metabolites and Inhibition of Benzo(a)pyrene-induced Immunosuppression by -Naphthoflavone¹

Departments of Pharmacology and Toxicology and Biostatistics, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0001

Several investigators have demonstrated that the humoral immune response of mice and splenocyte cultures was suppressed with benzo(a)pyrene [B(a)P] exposure. The mechanism of the B(a)P immunosuppression, however, has not been established. Since reactive metabolites of B(a)P, rather than the parent compound, have been shown to mediate the carcinogenic effects of B(a)P, it was hypothesized that the immunosuppression produced by B(a)P may also be mediated by its reactive metabolites. The objective of this investigation was to examine the role of B(a)P metabolism in the B(a)P-induced suppression of the in vitro humoral immune response. This was addressed by first determining if various B(a)P metabolites are capable of inhibiting the generation of antibody-forming cells (AFC) of splenocyte cultures. Addition of B(a)P or B(a)P-7,8-diol (2 x 10^-9 to 2 x 10^-5 M) to splenocyte cultures produced a similar dose-dependent suppression of the in vitro T-dependent AFC response to sheep red blood cells. In contrast, decreases in the AFC response and cell viability of cultures exposed to the 4,5-diol or 9,10-diol were only observed at 2 x 10^-5 M. Exposure of cultures to 3-hydroxy-B(a)P resulted in a significant decrease in the AFC response at 2 x 10^-6 and 2 x 10^-5 M. Slight decreases in the AFC response were observed with the addition of B(a)P-4,5-epoxide or B(a)P-6,12-dione at 2 x 10^-6 M, whereas a dramatic decrease in the AFC response, as well as a 45% decrease in cell viability, was obtained at 2 x 10^-5 M.

The second objective was to examine the effects of the cytochrome P-450 inhibitor, -naphthoflavone (ANF), on the B(a)P- and B(a)P-7,8-diol-induced suppression of the in vitro AFC response. Exposure of splenocyte cultures to 2 x 10^-5 M ANF did not affect the AFC response. Coincubation of splenocytes with ANF was observed to attenuate the suppressive effects of B(a)P and B(a)P-7,8-diol. This concentration of ANF was observed to inhibit the metabolism of [³H]B(a)P by splenocyte cultures to water soluble metabolites. Moreover, B(a)P metabolism by splenic microsomal preparations of untreated mice was inhibited by ANF. These findings suggest that the B(a)P-induced suppression of the in vitro AFC response is mediated by B(a)P metabolites generated by cytochrome P-450 present within splenocytes.

¹ Research supported in part by USPHS Grants ES05317 and ES03434, National Institute of Environmental Health Sciences Contract ES55094, and a Virginia Commonwealth University Grant in Aid.

² To whom requests for reprints should be addressed, at Pharmacology and Toxicology, P.O. Box 613, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0001.

³ Recipient of a Postdoctoral National Research Service Award (ES05317).

Received 10/23/86. Revised 2/ 4/87. Accepted 2/ 6/87.

This article has been cited by other articles:

				L. L. Allan, K. K. Mann, R. A. Matulka, H.-Y. Ryu, J. J. Schlezinger, and D. H. Sherr Bone Marrow Stromal-B Cell Interactions in Polycyclic Aromatic Hydrocarbon-Induced Pro/Pre-B Cell Apoptosis Toxicol. Sci., December 1, 2003; 76(2): 357 - 365. [Abstract] [Full Text] [PDF]

				J. van Grevenynghe, S. Rion, E. Le Ferrec, M. Le Vee, L. Amiot, R. Fauchet, and O. Fardel Polycyclic Aromatic Hydrocarbons Inhibit Differentiation of Human Monocytes into Macrophages J. Immunol., March 1, 2003; 170(5): 2374 - 2381. [Abstract] [Full Text] [PDF]

				B. Laupeze, L. Amiot, L. Sparfel, E. Le Ferrec, R. Fauchet, and O. Fardel Polycyclic Aromatic Hydrocarbons Affect Functional Differentiation and Maturation of Human Monocyte-Derived Dendritic Cells J. Immunol., March 15, 2002; 168(6): 2652 - 2658. [Abstract] [Full Text] [PDF]