Transplacental skin tumor initiation of Ha/ICR mice at different fetal ages.

The initiation of cells in fetal skin was studied by exposing pregnant Ha/ICR mice intragastrically to single doses of a carcinogen at different times during gestation. For comparison, adult mice were exposed to the same carcinogen in a similar manner. The carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA), was given at a dose of about 120 mg/kg in 0.2 ml sesame oil by gavage to 7-week-old pregnant females. The presence of initiated cells in the adult offspring was determined by topical application of 5.0 micrograms in 0.2 ml acetone of the skin tumor promoter tetradecanoyl-12-phorbol-13-acetate to the skin three times weekly beginning at 9 weeks of age. The yield of tumors was determined as a function of time during continuous promotion. Evidence of initiated cells was found in adults exposed transplacentally to DMBA as early as Day 9 of fetal development. The histological characteristics of the tumors and their temporal pattern of development were essentially the same for mice exposed at different stages of fetal development as they were for mice exposed to DMBA as adults. Male and female offspring exhibited approximately the same tumor yields. The use of [3H]DMBA and autoradiographs provided evidence that the cellular dose of DMBA was approximately equivalent at each stage of gestation and in adult skin. The results suggest that the number of initiated cells produced by a given dose of DMBA to the epidermis or fetal ectoderm is proportional to the number of cells in the tissue at the time of exposure.