Gene inactivation as a mechanism for the generation of variability in somatic cells cultivated in vitro

Abstract

It is proposed that a substantial proportion of cell culture variants result from repression or derepression of genetic information which specifies the synthesis of enzymes. The mechanism responsible for this process may be similar to the inactivation of euchromatic segments in Drosophila resulting from their transposition next to heterochromatin. This model could explain a number of confusing observations made in somatic cell culture systems. (1) The generally high mutation rate for markers in somatic cells. (2) The instability and high reversion rates of a number of genetic markers. (3) Failure of certain drug resistance markers to show the expected decreases in mutation rate with increase in ploidy levels. (4) Anomalous mutation induction kinetics, and lack of specificity of mutagenic agents. Means by which this model can be experimentally examined are proposed. They include: (a) correlation of late labeling patterns and transposition of genetic material with phenotypic changes suspected of having their basis in chromosomal inactivation. (b) Mutagenesis studies using markers which would be expected to show phenotypic variation due to chromosomal inactivation. (c) Studies of gene expression in somatic cell hybrids. (d) Examination of gene products from resistant cell lines suspected of arising from chromosomal inactivation. © 1977.