Huber B E, Brown N A
Res Commun Chem Pathol Pharmacol. 1985 Jul;49(1):17-34.
CD-1 Mice were treated with daily intraperitoneal injections of 10 or 100 micrograms/kg 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on pregnancy days 8, 9 and 10 or 11, 12 and 13 (early and late organogenesis). By the same regimen, the LD50 for TPA was about 450 micrograms/kg. TPA treatment induced embryomortality, fetal malformation and reduced fetal weight, generally in a dose-related manner. TPA treatment (100 micrograms/kg) was markedly more embryolethal on days 11-15 (68%/litter) than in early organogenesis (18%/litter). Renal malformations were observed in all treatment groups at a low incidence (about 5% of live fetuses) and in no case was the total incidence of malformations greater than 10%. There was little correlation between indications of maternal toxicity and the adverse outcomes of pregnancy, suggesting that TPA has direct embryotoxic effects. The relatively low incidence of anomalies is considered a paradox in light of the potent effects of TPA on cellular processes critical to embryogenesis.
在妊娠第8、9、10天或11、12、13天（早期和晚期器官形成期），对CD-1小鼠每日腹腔注射10或100微克/千克的12-O-十四烷酰佛波醇-13-乙酸酯（TPA）。按照相同方案，TPA的半数致死剂量（LD50）约为450微克/千克。TPA处理通常以剂量相关的方式诱导胚胎死亡、胎儿畸形并降低胎儿体重。TPA处理（100微克/千克）在第11 - 15天的胚胎致死率（68%/窝）明显高于早期器官形成期（18%/窝）。在所有处理组中均观察到低发生率（约占存活胎儿的5%）的肾脏畸形，且畸形总发生率在任何情况下均不超过10%。母体毒性指标与妊娠不良结局之间几乎没有相关性，这表明TPA具有直接的胚胎毒性作用。鉴于TPA对胚胎发育关键细胞过程具有强大作用，相对较低的畸形发生率被认为是一个矛盾现象。
