Schweizer J, Loehrke H, Goerttler K
Bull Cancer. 1978;65(3):265-70.
The classical 2-stage carcinogenesis experiment has been modified in that the carcinogen DMBA was applied to pregnant mother animals at different dose levels and different time intervals during pregnancy. Promotion with the phorbol ester TPA was performed as usual by application of the promoter on the back skin of mice of the F-1 generation. It can be shown that it is possible to initiate fetal epidermal cells by transmaternal route and to promote them to produce visible skin tumors post natum. Tumor promotion by TPA is not restricted to the epidermis, since a broad spectrum of tumors of internal organs can be demonstrated in the initiated and promoted animals. This more general promoting activity of TPA--which implies its absorption and distribution throughout the whole body--has not yet been described. In addition, especially sensitive phases during fetal life with regard to initiation of cells by the carcinogen can be demonstrated. These phases comprise the last third of pregnancy and coincide with a high proliferative activity and the onset of differentiation of the fetal epidermis. The results emphasize the important role of prenatal carcinogenesis and demonstrate the increased risk also to the human organism by either prenatal initiation or postnatal promotion.
经典的两阶段致癌实验已被改进，即致癌剂二甲基苯蒽（DMBA）在孕期以不同剂量水平和不同时间间隔应用于怀孕的母动物。如往常一样，通过在F-1代小鼠背部皮肤涂抹佛波酯TPA进行促癌。结果表明，经母体途径启动胎儿表皮细胞并使其在出生后发展为可见皮肤肿瘤是可能的。TPA的促癌作用并不局限于表皮，因为在启动和促癌的动物体内可发现多种内脏肿瘤。TPA这种更广泛的促癌活性——这意味着它被吸收并分布于全身——尚未见报道。此外，还可证明胎儿期存在对致癌剂启动细胞特别敏感的阶段。这些阶段包括孕期的最后三分之一，与胎儿表皮的高增殖活性和分化开始相吻合。这些结果强调了产前致癌的重要作用，并证明了无论是产前启动还是产后促癌，对人类机体的风险都会增加。
