Hypothesis: chemical carcinogenesis mediated by a transiently active carcinogen receptor

Biologically active small-molecular-weight compounds are actively transported into the cell nucleus by a specific receptor. This has been widely demonstrated for retinoids, polycyclic hydrocarbons (such as steroids), and dioxin. Thus, it is reasonable to assume that genotoxically active polycyclic hydrocarbons, and possibly all genotoxically active small-molecular-weight substances, exert their transformational effect in the cell nucleus via a specific receptor. I propose that the receptor is activated only at the end of the G(1) phase of the cell cycle and that the carcinogen receptor complex interferes directly with DNA synthesis, leading to mutations. This hypothesis may account for various characteristics of malignant growth, such as the organ specificity of carcinogens and the relationship between cell proliferation and malignant transformation. If so, it could form the basis for establishing a radioreceptor assay for carcinogens.