Urso P, Johnson R A
Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA 30310.
Immunopharmacology. 1987 Sep;14(1):1-10. doi: 10.1016/0162-3109(87)90003-8.
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.
苯并(a)芘是一种强效致癌物，会严重抑制在孕期（11至13天）接触该致癌物的小鼠后代的抗绵羊红细胞空斑形成细胞反应、混合淋巴细胞反应（传入T细胞功能）以及体内移植物抗宿主反应（传出T细胞功能）。免疫缺陷在出生后早期（1周）出现，并持续18个月。T细胞介导反应的异常促使我们研究在胚胎发育（15至19天）及出生后淋巴器官中T细胞及其亚群（Lyt 1+、Lyt 2+）的数量分布情况。此外，我们还研究了3至8个月大的后代及其脾细胞抵抗同基因纤维肉瘤（一种由苯并(a)芘诱导的肿瘤）细胞在体内生长的能力。我们的观察结果包括：(1) 在孕期晚期（19天）及出生后，胸腺中的T细胞及其亚群减少。(2) 在孕期，脾脏中的T细胞和Lyt 1+细胞减少，而出生后前者增加，对后者的影响则有所不同（增加和减少）。(3) 在胎儿肝脏中，T细胞减少，但Lyt 1+细胞未变。(4) Lyt 2+细胞在胎儿肝脏和脾脏中显著增加，但在前者中最为明显。(5) 在胎儿肝脏和脾脏中，Lyt 1/Lyt 2比值低于1.00或低于对照组，这种情况在脾脏中出生后持续30天。(6) 接触苯并(a)芘的后代或其脾细胞在抵抗转移肿瘤细胞的体内生长方面相对无效。这些结果表明，这种致癌污染物会导致T细胞及其亚群明显紊乱，这种紊乱在出生后至少可持续4周。这表明在个体发育过程中T细胞分化受到破坏，这可能对子宫内接触致癌物后抵抗肿瘤发生和生长的能力产生深远影响。
