Chromosomes bearing amplified genes are a preferential target of chemicals inducing chromosome breakage and aneuploidy. 1993

L Ottaggio, and S Bonatti, and Z Cavalieri, and A Abbondandolo
Laboratory of Mutagenesis, IST, Genoa, Italy.

Micronuclei were induced in V79 Chinese hamster cells and in PALA L and MTX M, two derivative cell lines harboring amplified genes, with 1,3-bis(2-chloroethyl)nitrosourea (BCNU) and vinblastine. Spontaneous and induced micronuclei were analyzed for the presence of centromeres by immunofluorescent CREST staining. Micronuclei formed in PALA L cells were also analyzed for the presence of amplified DNA by in situ hybridization with a CAD gene probe. Both cell lines containing amplified genes showed increased micronucleus induction by BCNU and vinblastine. The marker chromosome of PALA L cells was found to be a preferential target for both the clastogenic and the aneugenic action of the two chemicals. DNA amplification seems therefore to be a destabilizing factor of chromosomal structural integrity and mitotic segregation.

UI MeSH Term Description Entries
D009097 Multienzyme Complexes Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES. Complexes, Multienzyme
D002223 Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) An enzyme that catalyzes the formation of carbamoyl phosphate from ATP, carbon dioxide, and glutamine. This enzyme is important in the de novo biosynthesis of pyrimidines. EC 6.3.5.5. Carbamyl Phosphate Synthase (Glutamine),Carbamoyl-Phosphate Synthase (Glutamine),Carbamoylphosphate Synthetase II,Carbamyl Phosphate Synthase II,Carbamyl-Phosphate Synthase (Glutamine),Synthetase II, Carbamoylphosphate
D002330 Carmustine A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed) BCNU,1,3-Bis(2-Chloroethyl)-1-Nitrosourea,BiCNU,FIVB,N,N'-Bis(2-Chloroethyl)-N-Nitrosourea,Nitrumon
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004080 Dihydroorotase An enzyme that, in the course of pyrimidine biosynthesis, catalyzes ring closure by removal of water from N-carbamoylaspartate to yield dihydro-orotic acid. EC 3.5.2.3. Carbamoylaspartic Dehydrase,Dihydro-Orotase,Dihydro-Orotate Amidohydrolase,Amidohydrolase, Dihydro-Orotate,Dehydrase, Carbamoylaspartic,Dihydro Orotase,Dihydro Orotate Amidohydrolase
D005784 Gene Amplification A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. Amplification, Gene
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000782 Aneuploidy The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1). Aneuploid,Aneuploid Cell,Aneuploid Cells,Aneuploidies,Aneuploids,Cell, Aneuploid,Cells, Aneuploid

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