Alterations in immune function and CYP450 activity of adult male deer mice following exposure to either 7,12-dimethylbenz[a]anthracene or benzo[b]fluoranthene

Abstract

Adult male deer mice were exposed every other day for a period of 11 days to either 7,12-dimethylbenzanthracene (DMBA; CAS# 57-97-6) or benzo[b]fluoranthene (BbF; CAS# 205-99-2) (0, 0.3, 1, 3, 10, or 30 mg kg⁻¹). Immune endpoints assessed were lymphocyte proliferation, macrophage pinocytosis, and the antibody plaque-forming cell (PFC) response. Cytochrome P450 (CYP450) activity was assessed using ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-deethylase (PROD). Macrophage pinocytosis was not altered by either compound. Both T- and B-cell proliferations were significantly increased by DMBA at 0.3 or 1 mg kg⁻¹ and by BbF at 10 or 30 mg kg⁻¹, but decreased by DMBA at 30 mg kg⁻¹. Sheep red blood cell (SRBC)-specific-IgM production, as measured by the PFC response, was the most striking adverse immune effect observed and was significantly suppressed compared to control at all treatment concentrations for both compounds. EROD activity was markedly induced by DMBA at 30 mg kg⁻¹, while BbF produced induction at 1, 10, or 30 mg kg⁻¹. No marked effect on PROD activity was noted following DMBA treatment, but BbF-induced PROD activity at 1, 10, or 30 mg kg⁻¹. Unexpectedly, four of six mice in the 30 mg DMBA kg⁻¹ group did not survive to the end of the experiment, and one animal died in both the 3 and 10 mg kg⁻¹ treatments. The calculated LD₅₀ was 20.8 mg DMBA kg⁻¹. The PFC response in deer mice was a more sensitive endpoint than CYP450 activity, suggesting that utilization of CYP450 endpoints in risk assessment without assessment of immune function, specifically antibody production, might possibly underestimate the risk to wild rodents environmentally exposed to polycyclic aromatic hydrocarbons.

Keywords:

• PAH
• benzo[b]flouranthene
• DMBA
• immune
• toxicity
• deer mouse

Acknowledgments

The authors thank Jackie EuDaly for providing assistance in manuscript preparation. Funding was provided by the USEPA Office of Research and Development (RLD). Views represented here are those of the authors and do not reflect the views of the USEPA. The authors have no conflict of interest to declare. Technical Contribution No. 5253 of the Clemson University Experiment Station.