Complementation Studies in Murine/Human Hybrids Suggest Multiple Etiology for Increased Rate of Sister Chromatid Exchange in Mammalian Cells
Two mutational changes which occurred in culture and are associated with a high rate of sister chromatid exchange (SCE) pŉenotype have been identified in the L-A9 murine cell genome by means of complementation studies with somatic cell hybrids. Preliminary cyto-genetical evidence suggests that the retention of human autosome 6 (namely the region comprised between Xql2 and Xqter) or human autosome 19 is required in the hybrid metaphases for complementation to occur, independently of their being derived from normal human or Bloom syndrome (BS) cells. These data and other complementation studies previously reported by our group and by other investigators suggest that mammalian cells may possess several independent systems involved in the control of SCEs during chromatid replication. Thus, the high rate of SCE can be regarded as the common phenotype resulting from a variety of qualitative or quantitative changes affecting the mammalian cell genome. Bloom syndrome is evidently an example of homozygosity for a recessive mutation occurring in nature. The high SCE mutants found among rodent cells (as those seen in unstable rodent-human hybrid cells) are more likely the result of chromosomal loss or rearrangement occurring in culture at one or more of the genetic systems hypothesized above. The occurrence of complementation within or between the species barrier, following cell hybridization or cocultivation, indicates the recessive nature of the corresponding mutations and the possible homology of the relevant genetic systems in different mammalian species.
The Isolation of rodent clonal cell lines with a stable high rate of SCEs and the production of somatic cell hybrids between them and BS cells offer a promising experimental tool for studying the biology of SCEs in general and the genetics of BS in particular.
KeywordsSomatic Cell Hybrid Hybrid Line Hybrid Cell Line Bloom Syndrome Murine Cell Line
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