Mosaicism: The embryo as a target for induction of mutations leading to cancer and genetic disease

Journal Article · Sun Dec 31 04:00:00 EST 1995 · Environmental and Molecular Mutagenesis

DOI:https://doi.org/10.1002/em.2850250606· OSTI ID:272767

Mohrenweiser, H; Zingg, B ^[1]

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1. Lawrence Livermore National Lab., CA (United States)

Mosaicismhas been observed in both germinal and somatic tissues of several species, including humans. Mutational events occurring during early embryogenesis can give rise to an organism with a significant number of cells with the mutant genotype in one or more tissues. In the F{sub 1} generation, this event will usually be perceived as a de novo germinal mutation rather than a transmitted variant allele, unless significant effort is directed toward detecting the mosaicism. Similarly, mutations in oncogenes and tumor-suppressor genes in proliferating somatic cells can generate populations of cells that are at increased risk of transforming into tumor cells. The number of potential preneoplastic cells is larger when the mutagenic event occurs in early development than if it occurs in the mature adult. Experimental data confirm that treatment of the developing embryo or fetus with carcinogenic and mutagenic agents increases the cancer incidence in these animals and the frequency of mutations in the offspring of the animals that were exposed in utero. The available data are conclusive that the developing organism is at risk from exposure to mutagenic and carcinogenic agents. However, the data are insufficient to estimate the level of risk associated with similar exposures to the adult organism. The potential risk from exposure of the developing embryo is increased relative to the risk from adult exposure if the sensitivity of the individual cells to damage in the adult and the embryo are equivalent. It seems apparent that the potential risks of cancer and heritable disease following in utero exposure are sufficient to warrant additional attention. It is important to obtain data for estimating the relative contribution of in utero exposure to mutagenic and carcinogenic agents to the total health burden and for the subsequent development of appropriate regulations. 60 refs., 2 figs.

• Sponsoring Organization: USDOE
• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 272767
• Journal Information: Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl. 26 Vol. 25; ISSN 0893-6692; ISSN EMMUEG
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
EMBRYOS
EVALUATION
HEREDITARY DISEASES
MOSAICISM
NEOPLASMS