Carcinogenesis in relation to the stem-cell-mutation hypothesis.

From reports on fish, mice, rats, and humans, it can be concluded that at early developmental stages, especially stages before organogenesis, vertebrates are resistant to the induction of tumors by carcinogens. This conclusion and results on the molecular biology of chemical carcinogenesis in mice support the hypothesis that carcinogenesis of an organ is initiated by mutation of its stem cells formed during organogenesis. Convincing support for the existence of mutations that cause development of tumors is that heritable tumors are induced in mice and Drosophila by exposure of germ cells to radiation and chemicals. Various lines of evidence support the notion that tumor genes, which increase the predisposition of their carriers to develop tumors, are at least partly regulatory mutations. In this paper, the interrelation of tumorigenesis and teratogenesis, the high susceptibility of growing or regenerating organs to induction of tumors by carcinogens, and the latent period of induced neoplasms are discussed in relation to the stem-cell-mutation hypothesis.