X-ray induction of methotrexate resistance due todhfr gene amplification

Hahn, Peter; Nevaldine, Barbara; Morgan, William F.

doi:10.1007/bf01233191

Cited by 65 publications

(25 citation statements)

References 34 publications

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“…Although the observed induction of gross chromosome rearrangements in these clones did not influence the reciprocal exchange of homologous DNA sequences between sister chromatids, it is reasonable to assume that delayed chromosomal instability plays a significant role in gene mutation (7,16,32,40), gene amplification (17,18,33,38,50), cellular transformation (26,28), teratogenesis (15,35), and even carcinogenesis (13,30) after exposure of cells to DNA-damaging agents.…”

Section: Methodsmentioning

confidence: 91%

Delayed chromosomal instability induced by DNA damage.

Marder¹,

Morgan²

1993

Mol. Cell. Biol.

221

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DNA damage induced by ionizing radiation can result in gene mutation, gene amplification, chromosome rearrangements, cellular transformation, and cell death. Although many of these changes may be induced directly by the radiation, there is accumulating evidence for delayed genomic instability following X-ray exposure. We have investigated this phenomenon by studying delayed chromosomal instability in a hamsterhuman hybrid cell line by means of fluorescence in situ hybridization. We examined populations of metaphase cells several generations after expanding single-cell colonies that had survived 5 or 10 Gy of X rays. Delayed chromosomal instability, manifested as multiple rearrangements of human chromosome 4 in a background of hamster chromosomes, was observed in 29%o of colonies surviving 5 Gy and in 62% of colonies surviving 10 Gy. A correlation of delayed chromosomal instability with delayed reproductive cell death, manifested as reduced plating efficiency in surviving clones, suggests a role for chromosome rearrangements in cytotoxicity. There were small differences in chromosome destabilization and plating efficiencies between cells irradiated with 5 or

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Section: Methodsmentioning

confidence: 91%

Delayed chromosomal instability induced by DNA damage.

Marder¹,

Morgan²

1993

Mol. Cell. Biol.

221

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“…Mammalian cells treated with either radiation, DNA replication inhibitors, or other DNA-damaging agents show increased frequencies of gene amplification, suggesting chromosome breaks as initiating lesions (4,12,24,39). In fact, either a chromosome break at a fragile site or a site-specific chromosomal DNA double-strand break (DSB) induced by I-SceI endonuclease leads to gene amplification by initiating the formation of large palindromic chromosomes (9,37).…”

mentioning

confidence: 99%

Intrastrand Annealing Leads to the Formation of a Large DNA Palindrome and Determines the Boundaries of Genomic Amplification in Human Cancer

Tanaka

Cao

Bergstrom

et al. 2007

Molecular and Cellular Biology

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Amplification of large chromosomal regions (gene amplification) is a common somatic alteration in human cancer cells and often is associated with advanced disease. A critical event initiating gene amplification is a DNA double-strand break (DSB), which is immediately followed by the formation of a large DNA palindrome. Large DNA palindromes are frequent and nonrandomly distributed in the genomes of cancer cells and facilitate a further increase in copy number. Although the importance of the formation of large DNA palindromes as a very early event in gene amplification is widely recognized, it is not known how a DSB is resolved to form a large DNA palindrome and whether any local DNA structure determines the location of large DNA palindromes. We show here that intrastrand annealing following a DNA double-strand break leads to the formation of large DNA palindromes and that DNA inverted repeats in the genome determine the efficiency of this event. Furthermore, in human Colo320DM cancer cells, a DNA inverted repeat in the genome marks the border between amplified and nonamplified DNA. Therefore, an early step of gene amplification is a regulated process that is facilitated by DNA inverted repeats in the genome.

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“…The repeated units have been shown to be 200 to 500 kb in size (13,17). Much less is known about the DNA in DMs beyond the observation that they appear to be circular DNA when examined with the electron microscope (12) or with pulsed-field gel electrophoresis (PFGE) (11,20,21,28) and that their sizes range from 120 kb (30) to large enough to be visible microscopically (greater than 5 million bp).…”

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confidence: 99%