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Involvement of unstable chromosomal regions containing C-heterochromatin and fragile sites in the integration of amplifieddhfr domains

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Somatic Cell and Molecular Genetics

Abstract

A 10 −3 M methotrexate (MTX)-resistant variant (H 2),selected from the murine fibrosarcoma line B77-3T3/AA12, was characterized after 5 (H 2 MTX Res I) and 9 (H 2 MTX Res II) months of in vitro propagation in the presence of the drug. Southern blot hybridization of wild-type and H 2 MTX Res DNAs confirmed amplification of the dhfrgene without apparent rearrangements in its structure. Cytogenetic analysis revealed that double minutes (DMs) predominated in H 2 MTX Res I, whereas homogeneously staining regions (HSRs) were the main feature of H 2 MTX Res II cells. HSRs, shown to contain dhfrsequences by in situ chromosome hybridization, were localized within two rearranged chromosomes, designated as m1 and m2 because of their derivation from the marker chromosome m of AA12 cells. This chromosome, characterized by two interstitial C bands adjacent to two nonstaining gaps, was no longer observed in H 2 MTX Res II cells. A role for nonrandom involvement of chromosome m in the integration of amplified DNA is suggested by the finding of another HSR-chromosome, m3, derived from m, in an independent MTX Res clone (B 1).Rearrangement in one of the unstable C-band/gap regions of chromosome m is proposed as the unifying mechanism that may account for the outcome of the three HSR chromosomes observed.

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Authors and Affiliations

  1. Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Via Viotti 3/5-20133, Milan, Italy

    Paola Riva & Lidia Larizza

  2. Dipartimento di Farmacologia, Chemioterapia e Tossicologia, Università degli Studi di Milano, Italy

    Carlo De Giuli Morghen

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  1. Paola Riva
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  2. Carlo De Giuli Morghen
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  3. Lidia Larizza
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Riva, P., De Giuli Morghen, C. & Larizza, L. Involvement of unstable chromosomal regions containing C-heterochromatin and fragile sites in the integration of amplifieddhfr domains. Somat Cell Mol Genet 15, 377–385 (1989). https://doi.org/10.1007/BF01534889

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  • DOI: https://doi.org/10.1007/BF01534889

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