Clonal variants of constitutive heterochromatin of human fibroblasts after recovery from mitomycin treatment

Abstract

Presumptive clones of human skin fibroblast-like cells surviving mitomycin C treatments show a variety of intra- and interchromosomal rearrangements limited to the constitutive heterochromatic regions. Starting with a wild-type line polymorphic for chromosome no. 1 heterochromatin, we have observed clones with complete symmetry and varying degrees of asymmetry of the no. 1 heterochromatin, translocations of “excess” chromosome 1 heterochromatin to one no. 9 member, interstitial translocations to sites normally devoid of heterochromatin, and duplication of the Y chromosome long arm heterochromatin. In the case of the chromosome no. 1 pair, the extent of heterochromatin variation was quantitated to test the hypothesis that discrete classes of variants occur. There appear to be two types of variants: Those showing reciprocal changes between homologues (2 examples) and those showing a change in the amount of heterochromatin of a single homologue (5 examples). The latter group showed an approximately linear series of variants. Unequal cross-over following repair after damage from the alkylating agent is considered the most likely explanation for the observed changes, given the repetitive nature of DNA at these heterochromatic sites.