Immunomodulation by polyaromatic hydrocarbons in mice and murine cells

Area of Science:

• Immunology
• Environmental Toxicology
• Chemical Carcinogenesis

Background:

• Benzopyrenes are environmental pollutants with known carcinogenic properties.
• The immunomodulating effects of benzopyrenes are not fully understood.
• Antibody production is a critical component of the adaptive immune response.

Purpose of the Study:

• To investigate the immunomodulating mechanisms of benzo(a)pyrene (BaP) and benzo(e)pyrene (BeP).
• To assess the impact of BaP and BeP on antibody-generating systems in vitro and in vivo.
• To determine if the suppressive effects are related to carcinogenicity or cellular toxicity.

Main Methods:

• Utilized in vitro antibody generating systems, including T-dependent antibody (TDAb)-producing spleen cell cultures and polyclonal antibody-generating cultures.
• Administered BaP and BeP to cell cultures at various concentrations and time points.
• Exposed mice to BaP and BeP in vivo for 7 and 14 days.
• Measured plaque-forming cell responses to quantify antibody production.

Main Results:

• In vitro exposure to BaP and BeP caused dose- and time-dependent inhibition of TDAb and polyclonal antibody responses.
• Significant suppression was observed at low BaP concentrations (0.002 microgram/ml) and moderate BeP concentrations (2 microgram/ml).
• In vivo exposure to BaP and BeP significantly suppressed both TDAb and polyclonal antibody responses, with BaP causing up to 98% suppression of TDAb response after 14 days.

Conclusions:

• Benzopyrenes exert suppressive effects on antibody production through multicellular mechanisms.
• These immunomodulatory effects are distinct from the carcinogenic properties of benzopyrenes.
• The observed suppression is not solely attributable to general cellular toxicity.