Mosaicism: the embryo as a target for induction of mutations leading to cancer and genetic disease.
Mosaicism, the existence of "patches" of cells with a genetic constitution that differs from that of other cells of an organism, has 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. If this event occurs in a precursor of the germ cells, the mutation can be transferred to subsequent generations. In the F1 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 exposures in utero, relative to either the background (spontaneous) level of risk or risk associated with similar exposures to the adult organism.(ABSTRACT TRUNCATED AT 250 WORDS)
Mohrenweiser
H
H
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Zingg
B
B
D000818:Animals; D005314:Embryonic and Fetal Development / Q000235:genetics; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D009030:Mosaicism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D012307:Risk Factors