Subnormal expression of cell‐mediated and humoral immune responses in progeny disposed toward a high incidence of tumors afterin uteroexposure to benzo[a]pyrene

Abstract

Pregnant mice were exposed to 150 micrograms benzo[a]pyrene (BaP) per gram of body weight during fetogenesis (d 11-17 of gestation) and the progeny were assayed for humoral and cell mediated immune responses at different time intervals after birth. Immature offspring (1-4 wk) were severely suppressed in their ability to produce antibody-(plaque-) forming cells (PFC) against sheep red blood cells (SRBC) and in the ability of their lymphocytes to undergo a mixed lymphocyte response (MLR). Lymphocytes from these progeny showed a moderate to weak capacity to inhabit production of colony-forming units (CFU) in host spleens following transfer with semiallogeneic bone marrow (BM) cells into lethally X-irradiated recipients syngeneic to the BM (in vivo graft-versus-host response, GVHR). A severe and sustained suppression in the MLR and the PFC response occurred from the fifth month up to 18 mo. The in vivo GVHR, also subnormal later in life, was not as severely suppressed as the other two parameters. Tumor incidence in the BP-exposed progeny was 8- to 10-fold higher than in those encountering corn oil alone from 18 to 24 mo of age. These data show that in utero exposure to the chemical carcinogen BaP alters development of components needed for establishing competent humoral and cell-mediated functions of the immune apparatus and leads to severe and sustained postnatal suppression of the defense mechanism. The immunodeficiency exhibited, particularly in the T-cell compartment (MLR, GVHR), before and during the increase in tumor frequency, may provide a favorable environment for the growth of nascent neoplasms induced by BaP.

Perinatal Exposure to Δ9-Tetrahydrocannabinol Triggers Profound Defects in T Cell Differentiation and Function in Fetal and Postnatal Stages of Life, Including Decreased Responsiveness to HIV Antigens

“…Studies from our laboratory and others have shown that perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces thymic atrophy and alterations in thymic subsets that can still be detected several days after exposure (Holladay, 1999;Camacho et al, 2004). In addition, others have shown that mice that had been exposed to chlordane during fetal development had decreased delayed-type hypersensitivity and mixed-lymphocyte reactivity as adults (Urso and Gengozian, 1984). The current study demonstrates for the first time that marijuana abuse during pregnancy may affect the immune response of the fetus that could last into the adulthood.…”

Alterations in fetal thymic and liver hematopoietic cells as indicators of exposure to developmental immunotoxicants.

“…This latter effect in particular has not been observed in adult mice after similar dosing with chlordane. Similar to chlordane, the offspring of pregnant mice treated with the polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (B[a]P), showed long-term (e.g., still present at 18 months of age) depression of antibody, graft-versus-host, and mixed lymphocyte responses (5). Similar changes in mice after gestational exposure to additional immunotoxic compounds have been associated with reduced ability of the animals to withstand immunologic challenge (e.g., syngeneic tumor cells or bacterial, viral, or parasitic agents) later in life (6)(7)(8).…”

Prenatal immunotoxicant exposure and postnatal autoimmune disease.

“…(7). Mice exposed to chlordane during fetal life also display reduced numbers of granulocyte-macrophage colony-forming units and colony-forming units in the spleen at 200 days of age (8) as well as long-term depression of both delayed-type hypersensitivity and mixed lymphocyte reactivity (9). It is noteworthy that these immune effects are either reduced or not observed in adult mice exposed to chlordane at dose levels equal to those given to the pregnant mice (8 (20).…”