title: Gene amplification and gene deletion are induced at different rates in V79/AP4 Chinese hamster cells.
abstract: The effect of mitomycin C (MMC) treatment on gene amplification and gene deletion induction in a V79/AP4 Chinese hamster cell line was investigated. Spontaneous and induced cellular variants resistant to N-phosphonacetyl-L-aspartate (PALA), which selects for carbamyl-P-synthetase, aspartate transcarbamylase and dihydroorotase (CAD) gene amplification events, and to intermediate concentrations of 2,6-diaminopurine (DAP), which selects for adenine phosphoribosyl transferase (aprt) gene deletion events, were isolated. The molecular analysis of spontaneous and induced PALA- and DAP-resistant clones showed that while in the former the CAD gene was amplified, in the latter both mutations and deletions occurred at the aprt gene. These results indicate that MMC favored the rise of gene amplification rather than gene deletion events, and suggest that aberrant DNA replication processes were responsible for the observed gene amplification.
authors.affiliation: Genetica e Biochimica Tossicologica, Istituto di Mutagenesi e Differenziamento, CNR, Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Vatteroni
authors.forename: A
authors.initials: A
authors.lastname: Piras
authors.forename: A
authors.initials: A
authors.lastname: Moretti
authors.forename: G
authors.initials: G
authors.lastname: Rainaldi
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000235:genetics; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004080:Dihydroorotase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D005784:Gene Amplification; D017353:Gene Deletion; D016685:Mitomycin / Q000633:toxicity*; D009097:Multienzyme Complexes / Q000235:genetics; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C033626:CAD trifunctional enzyme; D009097:Multienzyme Complexes; D009153:Mutagens; D001224:Aspartic Acid; D015075:2-Aminopurine; C007300:2,6-diaminopurine; D016685:Mitomycin; C013195:sparfosic acid; D004247:DNA; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); D010746:Phosphonoacetic Acid