Effects of transplacental exposure to diethylstilbestrol on carcinogenic susceptibility during postnatal life in hamster progeny.

Prenatal exposure to a single dose of diethylstilbestrol (DES) produced a significant increase in carcinogenic response of hamster progeny that were subsequently subjected to the carcinogenic stimulus of 7,12-dimethylbenz(a)anthracene (DMBA) during postnatal life. The compounds were administered according to the following schedules. The pregnant animals (second group) received a single dose of DES, 10 mg/kg, on Day 14 of gestation. Postnatally, at 6 weeks of age, the progeny were given DMBA, 25 mg/kg p.o., twice weekly for 8 weeks. The first group received DMBA at 6 weeks of age, 30 mg/kg p.o., twice weekly for 18 weeks. The progeny exposed to DES prenatally and DMBA postnatally (DES-DMBA-exposed progeny) developed a greater multiplicity of tumors per tumor-bearing animal (p less than 0.001) and higher rates of neoplasms of the reproductive tract, e.g., ovarian and uterine tumors, mammary gland and forestomach tumors, and dermal melanomas. The prenatally DES-exposed progeny also had significantly higher incidences of malignant tumors, e.g., carcinomas of the mammary gland (p less than 0.001) and carcinomas of the forestomach (p less than 0.001), than did the hamsters given DMBA alone during postnatal life. Endocrine imbalance produced by exposure in utero may heighten the sensitivity of the progeny to development of neoplasms after a challenge with carcinogenic stimuli in adult life. The significance of these experimental data to the human situation is discussed.