Presence of CD4(+) SP and DP (gammadelta, alphabeta) T-Cells Expressing BPDE-DNA Adducts in Progeny of Mouse Dams Exposed to Benzo(alpha) pyrene at Mid-Gestation.
After one exposure of C3H/HeJ pregnant females (at mid-gestation) to B(alpha) P (at 150 mu g/g BW), their progeny evidenced suppression of both humoral and cell-mediated immunity, as well as quantitative deficiencies in the levels of Lyt1(+) and Lyt2(+)cells, and CD4(+) CD8(+), V(gamma 3)(+), V(gamma delta)(+), and V(alpha beta)(+)T-cells. We hypothesized that these conditions could be a result, in part, of covalent binding of BPDE to DNA within these cells. To test this, antiserum to BPDE-DNA was generated in rabbits; after multiple purification steps, an anti-BPDE-DNA (rendered approximately 99.5% specific for BPDE-DNA and did not react with free BPDE or DNA antigens at dilutions even of < 1:50) antiserum was isolated. Flow cytometry and immunofluorescence analyses showed the adduct was present in CD4(+) cells of progeny fetal and in both post-natal thymus and spleen tissues. Using a [(32)P]-post-labelling method, adduct was also detected in samples of fetal liver during the period from Day 15 to 18 gestation. Surprisingly, it was found that thymus cells from B(alpha)P-exposed mice not exhibiting the adduct could severely suppress allogeneic mixed lymphocyte responses, while those in which the adduct was detected caused had a more pronounced suppression. We suspect from the findings here that the presence of BPDE-DNA adducts in T-cells contributes to, but is not necessarily the causa sola for, the immunosuppression that develops in the offspring of pregnant mothers who are exposed to B(alpha)P (among many other agents) via smoking, ingestion, or inhalation of environmental pollution.
Moolenaar-Wirsiy
Pamela J
PJ
Department of Biology, Clark-Atlanta University, Atlanta, Georgia, USA.
Wirsiy
Yungri G
YG
Urso
Paul
P