Early changes in T lymphocytes and subsets of mouse progeny defective as adults in controlling growth of a syngeneic tumor after in utero insult with benzo(a)pyrene.
Benzo(a)pyrene, a potent carcinogen, severely suppresses the anti-SRBC plaque-forming cell response, the mixed lymphocyte response (afferent T cell function), and an in vivo graft-vs.-host response (efferent T cell function) of mouse progeny exposed to the carcinogen during gestation (11 to 13 days). Immunodeficiency occurs early after birth (1 week) and persists for 18 months. The abnormalities in the T cell-mediated responses led us to examine the quantitative profile of T cells and subsets (Lyt 1+, Lyt 2+) present in the lymphoid organs during fetogenesis (15 to 19 days) and postnatally. In addition, we examined the ability of 3- to 8-month-old progeny and their spleen cells to resist the in vivo growth of cells from a syngeneic fibrosarcoma (a tumor that had been induced by benzo(a)pyrene). Our observations included: (1) Depletion of T cells and subsets in the thymus late (19 days) in gestation and postnatally. (2) Depleted T and Lyt 1+ cells in the spleen during gestation, while postnatally the former were enhanced and the effect on the latter was variable (enhancement and reduction). (3) In the fetal liver, the T cells were reduced, but the Lyt 1+ cells were unchanged. (4) The Lyt 2+ cells were strikingly enhanced in the fetal liver and spleen, but most dramatically for the former. (5) The Lyt 1/Lyt 2 ratio was less than 1.00 or controls in the fetal liver and spleen, a condition which persisted for 30 days postnatally in the latter organ. (6) Benzo(a)pyrene-exposed progeny or their spleen cells were relatively ineffective in resisting in vivo growth of transferred tumor cells. These results show that this carcinogenic pollutant induces a marked disorientation of T cells and subsets which can persist for at least 4 weeks postnatally. This suggests disruption of T cell differentiation during ontogenesis which may have profound implications on the ability to resist induction and growth of neoplasias after in utero exposure to the carcinogen.
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology*; D009929:Organ Size / Q000187:drug effects; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects*
D001564:Benzo(a)pyrene