Ng Sheung P, Silverstone Allen E, Lai Zhi-Wei, Zelikoff Judith T
New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, New York 10987, USA.
Toxicol Sci. 2006 Jan;89(1):135-44. doi: 10.1093/toxsci/kfj006. Epub 2005 Oct 5.
Epidemiologic evidence suggests that prenatal exposure to intact (unfractionated) cigarette smoke (CS) increases the incidence of cancer in the offspring. A toxicology study was carried out to examine the effects and underlying mechanisms of prenatal exposure to mainstream cigarette smoke (MCS) on offspring resistance to tumor challenge and surveillance mechanisms critical for the recognition and destruction of tumors. Pregnant B6C3F1 mice were exposed by inhalation to MCS for 5 days/week (4 h/day from gestational day 4 to parturition). Smoke-induced effects on offspring-host resistance to transplanted tumor cells; natural killer (NK) cell and cytotoxic T-lymphocyte (CTL) activity; cytokine levels; lymphoid organ immune cell subpopulations; and histology-were examined in 5-, 10- and 20-week-old male and female offspring. At a concentration of smoke roughly equivalent to smoking <1 pack of cigarettes/day, prenatally exposed male offspring challenged at 5 week of age with EL4 lymphoma cells demonstrated a greater than two-fold increase in tumor incidence (relative to age-/gender-matched air-exposed offspring); tumors in prenatally smoke-exposed pups also grew significantly faster. Cytotoxic T-lymphocyte activity in the smoke-exposed 5- and 10-week-old male pups was significantly less than that of the age- and gender-matched controls. No effects of prenatal CS exposure were observed on offspring NK activity, cytokine levels, lymphoid organ histology, or immune cell subpopulations. Results demonstrated that exposure of pregnant mice to a relevant dose of MCS decreased offspring resistance against transplanted tumor cells and persistently reduced CTL activity in prenatally exposed pups. This study provides biological plausibility for the epidemiologic data indicating that children of mothers who smoke during pregnancy have a greater risk of developing cancer in later life.
流行病学证据表明，产前暴露于完整（未分级）香烟烟雾（CS）会增加后代患癌几率。开展了一项毒理学研究，以检验产前暴露于主流香烟烟雾（MCS）对后代肿瘤挑战抗性以及对肿瘤识别与破坏至关重要的监测机制的影响和潜在机制。怀孕的B6C3F1小鼠通过吸入方式，每周5天（从妊娠第4天至分娩，每天4小时）暴露于MCS中。研究了烟雾对5周龄、10周龄和20周龄的雄性和雌性后代的宿主对移植肿瘤细胞的抗性、自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）活性、细胞因子水平、淋巴器官免疫细胞亚群以及组织学的影响。在烟雾浓度大致相当于每天吸食不到1包香烟的情况下，5周龄时用EL4淋巴瘤细胞攻击的产前暴露雄性后代的肿瘤发病率比年龄和性别匹配的空气暴露后代高出两倍多；产前暴露于烟雾的幼崽中的肿瘤生长也明显更快。烟雾暴露的5周龄和10周龄雄性幼崽中的细胞毒性T淋巴细胞活性明显低于年龄和性别匹配的对照组。未观察到产前CS暴露对后代NK活性、细胞因子水平、淋巴器官组织学或免疫细胞亚群有影响。结果表明，怀孕小鼠暴露于相关剂量的MCS会降低后代对移植肿瘤细胞的抗性，并持续降低产前暴露幼崽的CTL活性。这项研究为流行病学数据提供了生物学合理性，表明孕期吸烟母亲的孩子在晚年患癌风险更高。
