Changes in biologic and/or immunologic parameters induced by intratracheal instillation of pregnant mice with benzo(α)pyrene are potentially confounded by anesthesia

Abstract

Benzo(α)pyrene (B(α)P) is a potent multiorgan carcinogen released into the atmosphere from commercial, domestic, and industrial sources. Studies using animal models have shown that giving B(α)P parenterally to pregnant animals (i.e., dams) led to increased tumor frequency and sensitivity to tumorigenesis in their progeny. The authors’ studies also showed that the progeny of the B(α)P-exposed dams displayed increased deficiencies in cell-mediated and humoral immune functions, changes among T-cell subsets in developing lymphoid tissues, and significant expression of B(α)P-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adducts in thymic, splenic, and (fetal) liver tissues. The authors evaluated whether similar biologic/immunologic effects of B(α)P seen earlier in parenterally exposed mouse dams (and offspring) occurred if dams were exposed to B(α)P via the lungs. Pregnant dams were subjected to intratracheal instillation of B(α)P (at 1 mg/ml corn oil, 0.1 ml/instillate) beginning on day 11 of pregnancy (GD 11) and again on GDs 12 and 14. In each case, the dams were anesthetized with metofane. Other dams were left untreated (controls), anesthetized only, or anesthetized and then instilled with vehicle. Effects of the B(α)P exposures included lower dam body weights during gestation, decreased postbirth pup survival, increased pup tumor frequency, and decreased mixed-lymphocyte responses by pup lymphocytes. These studies also revealed that metofane imparted effects on the dams and progeny. These effects equaled the B(α)P treatments alone; in other instances, the metofane had no impact, and thus questions the observed biologic/immunologic effects of B(α)P induced in pregnant mice (and their progeny), which might have been confounded by use of this (or potentially other) anesthesia.

Keywords::

• Benzo(α)pyrene
• intratracheal instillation
• methoxyflurane
• metofane
• MLR

Acknowledgments

The authors thank Ms. Nicole Mashburn for computer and editorial assistance.

Declaration of interest

This work was supported by funds from The United States Environmental Protection Agency (grant R815813) and by funds provided by The United States Agency for International Development (grant PCE-5053-G-00-3062). The authors are alone responsible for the content and writing of the paper.