Paulson R B, Shanfeld J, Vorhees C V, Cole J, Sweazy A, Paulson J O
Department of Oral Biology, College of Dentistry, Ohio State University, Columbus 43210-1241.
Teratology. 1994 Apr;49(4):293-305. doi: 10.1002/tera.1420490409.
Three dosages of Smokeless Tobacco (ST) extract were given to pregnant Sprague-Dawley rats by oral gavage on gestational days (GD) 6-20. The three dosages contained ST extract equivalent to 1.33 mg/kg nicotine (STD-1), 4.0 mg/kg nicotine (STD-2), and 6.0 mg/kg nicotine (STD-3). Dams were intubated three times per day at 8 a.m., 11 a.m., and 2 p.m., providing total daily ST dosages of 4 mg/kg, 12 mg/kg, and 18 mg/kg, respectively. Controls received equivalent volumes of water by gavage. Dams were allowed to deliver, and all biological mothers raised their own pups. On postnatal day 1 (PND 1), litters were culled to 4 +/- 1 females and 4 +/- 1 males. Weights, physical landmark development, and behavioral performance of pups were monitored during pre- and post-weaning periods. Behavioral tests included surface righting, negative geotaxis, swimming development, open field activity, and active avoidance in shuttle box. Our results show that the two higher doses resulted in reduced maternal weight gain. During the pre-weaning period, significant pup weight reductions were noted in the STD-2 pups until PND6, and in the STD-3 group until PND15. In the STD-1 group no statistically significant weight reduction was noted on PNDs 1 and 3, but starting with PND6, pup weights surpassed control group weights. This weight difference persisted throughout the post-weaning period also (P < .05 on PND30 and PND42). The STD-3 pup weights continued to be consistently and significantly (P < .05) reduced throughout the post-weaning period (except on PND24); likewise, the STD-2 pups continued to have lower weights, but at a significant level (P < .05) on PND30 only. The incidence of deaths was increased in a dose-related manner. No significant differences were noted for pinna detachment and incisor eruption; however ST-treatment was significant in affecting earlier eye opening and vaginal patency. N significant ST treatment effects were seen on negative geotaxis, but for surface righting a decreased success rate was noted for the ST-treated groups. Significant differences were noted in swimming development, with the STD-2 pups performing best. Open field activity, as expected, increased from the pre-weaning to post-weaning periods. During the pre-weaning period the STD-3 pups were more active, and during post-weaning the STD-1 pups were more active, but no differences were noted in vertical activity or in the number of stereotypical movements. No treatment-related differences were noted in the active avoidance shuttle box.(ABSTRACT TRUNCATED AT 400 WORDS)
在妊娠第6至20天,通过口服灌胃法给怀孕的斯普拉格-道利大鼠给予三种剂量的无烟烟草(ST)提取物。这三种剂量所含的ST提取物相当于1.33毫克/千克尼古丁(STD - 1)、4.0毫克/千克尼古丁(STD - 2)和6.0毫克/千克尼古丁(STD - 3)。母鼠每天于上午8点、11点和下午2点进行三次插管给药,每日ST总剂量分别为4毫克/千克、12毫克/千克和18毫克/千克。对照组通过灌胃给予等量的水。母鼠正常分娩,所有生母哺育自己的幼崽。在出生后第1天(PND 1),将每窝幼崽挑选至4±1只雌性和4±1只雄性。在断奶前后监测幼崽的体重、身体标志性发育和行为表现。行为测试包括表面翻正反射、负趋地性、游泳发育、旷场活动以及穿梭箱中的主动回避。我们的结果表明,较高的两种剂量导致母鼠体重增加减少。在断奶前阶段,STD - 2组幼崽在PND6之前体重显著降低,STD - 3组幼崽在PND15之前体重显著降低。在STD - 1组中,PND1和PND3时未观察到统计学上显著的体重降低,但从PND6开始,幼崽体重超过对照组体重。这种体重差异在断奶后阶段也持续存在(PND30和PND42时P < 0.05)。在整个断奶后阶段(PND24除外),STD - 3组幼崽体重持续且显著(P < 0.05)降低;同样,STD - 2组幼崽体重持续较低,但仅在PND30时达到显著水平(P < 0.05)。死亡发生率呈剂量相关增加。在耳廓分离和门齿萌出方面未观察到显著差异;然而,ST处理对更早睁眼和阴道开放有显著影响。在负趋地性方面未观察到显著的ST处理效应,但对于表面翻正反射,ST处理组的成功率降低。在游泳发育方面观察到显著差异,STD - 2组幼崽表现最佳。正如预期的那样,旷场活动从断奶前到断奶后阶段增加。在断奶前阶段,STD - 3组幼崽更活跃,在断奶后阶段,STD - 1组幼崽更活跃,但在垂直活动或刻板运动次数方面未观察到差异。在主动回避穿梭箱中未观察到与处理相关的差异。(摘要截断于400字)