Dibenzo[def,p]chrysene (DBC) suppresses antibody formation in spleen cells following oral exposures of mice

Abstract

Dibenzo[def,p]chrysene (DBC) is a potent environmental carcinogen in rodents, fish, and human cells examined in culture. There are numerous similarities between the patterns of cytochrome P-450 (P450) activation of DBC and its covalent binding to DNA and proteins with another polycyclic aromatic hydrocarbon (PAH), 7,12-dimethylbenz[a]anthracene (DMBA). Our lab has previously shown that DMBA produces immunosuppression in rodents and human cell systems. Therefore, the purpose of these studies was to examine the immunotoxicity of DBC in a rodent model that was found to be sensitive to the immunosuppressive effects of DMBA. Data showed that DBC had similar potency to DMBA in producing suppression of a T-dependent antibody response (TDAR) and altered spleen cell subsets in a similar manner as DMBA when DMBA was given by gavage for 5 d in corn oil to mice at doses of 1-100 mg/kg total cumulative doses. T-cell-independent antigen (TNP-Ficoll) responses were quantitatively less sensitive to DBC suppression. It was also found that as with DMBA, DBC produced a persistent immunosuppression, which lasted for at least 4 wk following dosing with a novel pill method for self-administration of DBC. In conclusion, DBC appears to possess many of the same characteristics of DMBA in terms of its immunotoxicity.

Figure 1

Dose-dependent suppression of the T-dependent antibody response (TDAR) to SRBC by DBC given via gavage in corn oil for 5 consecutive days to mice and spleen cells were examined for in vitro antibody production two days later. Results are Mean ± SEM, (*) statistically significant compared to control at p ≤.05.

Figure 2

Cell surface marker expression for viable (as defined by FALS) CD45⁺ spleen cells recovered on day 7 for mice examined in Figure 1. The percentage of cells obtained for each marker in controls were as follows: CD3⁺=25.2±3.6, CD4⁺=14.3±2.3, CD8⁺=12.2±1.5, CD19⁺=64.1±2.2, Mac-1⁺=1.5±0.3, and NK=3.6±0.6. Results shown are Mean ± SD for 4 replicate animals. * p ≤ .05

Figure 3A

Suppression of the TDAR to SRBC by 10 mg/kg total cumulative dose of DBC given via gavage. Murine spleen cells were analyzed for persistence of immunosuppression 4 weeks after the last dose of DBC. Results are Mean ± SEM and statistical significance is determined at p ≤.05 compared to a corn oil pill (*).

Figure 3B

Results (Mean ± SD) are as described for the same group of murine spleens cells examine in Fig 3A, with the exception that TNP-Ficoll was used as the test antigen. *p ≤.05.

Figure 4

Cell surface marker data for murine spleen cells examined 4 weeks after last exposure to DBC (Figures 3A and 3B) given via gavage at a total cumulative dose of 10 mg/kg . Values are expressed as Mean ± SD for 4 replicate animals. p ≤ .05.

Figure 5A

Dose-dependent suppression of the TDAR to SRBC when mice were examined two days after the last of five daily doses of DBC given as a pill containing test agent and self-administered (eaten) by mice. Results are the Means ± SEM for 5 mice per group determined to be statistically significant at the level of p ≤.05 (*)

Figure 5B

Persistent immunosuppression of TDAR by DBC. As in Fig. 5A, except mice were held for four weeks after their last dose of DBC. Results are the Means ± SEM for 5 mice per group determined to be statistically significant at the level of p ≤.05 (*)