Relationship Between Alkylation Sites and Induction of Dominant Lethals and Heritable Translocations in Mice

摘要

Production of dominant lethals and heritable translocations appears to be determined by the degree of stability of alkylation products within the chromosome. If repair is not effected in the fertilized eggs and the alkylation products persist to the time of pronuclear chromosome replication or early cleavage divisions, they lead to chromatid-type aberrations and eventually to lethality. The production of heritable translocations requires a transformation of unstable alkylation products into suitable intermediate lesions. These lesions are then converted into chromosome exchanges prior to the time of pronuclear chromosome replication. Thus, dominant lethals result from both chromatid- and chromosome-type aberrations while heritable translocations results primarily from the latter type. It is inherent in our interpretation of the mechanism that the production of chromosome- and chromatid-type aberrations by a chemical mutagen are not necessarily mutually exclusive. 17 refs., 1 tab. (ERA citation 10:037835)