Carcinogenesis, Vol. 22, No. 1, 141-145,
January 2001
© 2001 Oxford University Press
CANCER BIOLOGY |
Gene amplification in fibroblasts from ataxia telangiectasia (AT) patients and in X-ray hypersensitive AT-like Chinese hamster mutants
Istituto di Genetica Biochimica ed Evoluzionistica, CNR, Via Abbiategrasso 207, 27100 Pavia,
1 Dipartimento di Genetica e Microbiologia `A.Buzzati Traverso', Università di Pavia, Via Abbiategrasso 207, 27100 Pavia,
2 Dipartimento di Biologia Cellulare e dello Sviluppo `A.Monroy', Università di Palermo, 90128 Palermo and
3 Dipartimento di Biologia e Genetica per le Scienze Mediche, Università di Milano, Via Viotti 3/5, 20133 Milano, Italy
In search of functions involved in the regulation of gene amplification, and given the relevance of chromosome breakage in initiating the process, we analyzed the gene amplification ability of cells hypersensitive to inducers of DNA double-strand breaks and defective in cell cycle control: two human fibroblast strains derived from patients affected by ataxia telangiectasia (AT) and two hamster mutant cell lines belonging to complementation group XRCC8 of the rodent X-ray-sensitive mutants. These mutants are considered hamster models of AT cells. To measure gene amplification, the frequency and the rate of occurrence of N-(phosphonacetyl)-L-aspartate resistant cells were determined. In both hamster mutants, these two parameters were increased by about an order of magnitude compared with parental cells, suggesting that amplification ability was increased by the genetic defect. In primary AT fibroblasts, as in normal human fibroblasts, gene amplification was undetectable and a block in the G1 phase of the cell cycle was induced upon PALA treatment. These results suggest that in AT fibroblasts, where only the ATM gene is mutated, ATM-independent mechanisms prevent gene amplification, while, in the immortalized hamster cell lines, which are already permissive for gene amplification, the AT-like defect increases the probability of gene amplification.
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