Effects of postnatal administration of tumour-promoting barbiturates on the development of tumours initiated by prenatal exposure of fetal rats and mice to N-alkylnitrosoureas.

Prenatal administration of chemical carcinogens followed by postnatal application of tumour promoters can result in tumour formation at sites where no tumours would occur in the absence of promotion. Three different epithelia in mice and rats have been shown to be susceptible to transplacental initiation by N-nitroso compounds or polynuclear aromatic hydrocarbons, yielding potentially neoplastic cells in fetal tissues which can remain latent indefinitely until stimulated to proliferate by postnatal exposure to a promoting agent. These include epidermal squamous epithelium in mice, renal cortical epithelium in mice, and thyroid follicular epithelium in both mice and rats. The fact that effective promoters of carcinogenesis in nonsquamous epithelia include drugs such as phenobarbital that are administered to humans in high doses for prolonged periods suggests that prenatal initiation followed by postnatal promotion may pose significant risks for humans, and should be considered in designing epidemiological searches for etiological factors that contribute to the incidence of epithelial tumours in man.