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Carcinogenesis in relation to the stem-cell-mutation hypothesis
Abstract:
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.
Insights
Vertebrates are resistant to carcinogens during early development. Tumor development is initiated by stem cell mutations during organogenesis, supported by heritable tumor induction studies.
Area of Science:
- Developmental Biology
- Cancer Research
- Molecular Biology
Background:
- Early developmental stages in vertebrates, particularly before organogenesis, exhibit resistance to carcinogen-induced tumors.
- Studies on chemical carcinogenesis in mice provide insights into the molecular mechanisms underlying tumor formation.
- Heritable tumors in mice and Drosophila, induced by germ cell exposure to radiation and chemicals, offer evidence for mutations causing cancer.
Purpose of the Study:
- To explore the hypothesis that organ carcinogenesis is initiated by stem cell mutations during organogenesis.
- To discuss the relationship between tumorigenesis and teratogenesis.
- To examine the susceptibility of growing or regenerating organs to carcinogens and the latent period of induced neoplasms in the context of the stem-cell-mutation hypothesis.
Main Methods:
- Review of existing reports on tumor induction by carcinogens in various species (fish, mice, rats, humans).
- Analysis of molecular biology data related to chemical carcinogenesis in mice.
- Examination of evidence for heritable tumor induction and the nature of tumor genes.
Main Results:
- Vertebrates are resistant to carcinogen-induced tumors before organogenesis.
- Carcinogenesis of an organ is hypothesized to be initiated by mutations in stem cells formed during organogenesis.
- Tumor genes, predisposing carriers to tumors, are suggested to be partly regulatory mutations.
Conclusions:
- The stem-cell-mutation hypothesis provides a framework for understanding tumor development.
- The interrelation of tumorigenesis and teratogenesis, organ susceptibility, and latent periods are consistent with stem cell mutation initiation.