Chemically induced mutagenesis in a shuttle vector with a low-background mutant frequency.

Drinkwater, Norman R.; Klinedinst, Donna

doi:10.1073/pnas.83.10.3402

Cited by 76 publications

(34 citation statements)

References 23 publications

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“…Targeted mutagenesis is also indicated for 1-NOP-induced base substitutions in-VOL. 8,1988 on (Table 3) showed that 13% of the base changes involved A T base pairs, and Kinouchi and Ohnishi (19) recently demonstrated with bacterial nitroreductases that a minor adduct formed by 1-NP involved deoxyadenosine. Therefore, we consider the base substitutions induced by these two carcinogens to be targeted to adducts rather than being the result of apurinic sites (24).…”

Section: Discussionmentioning

confidence: 95%

“…The latter hypothesis is supported by recent studies on the specific mutational changes needed to activate specific oncogenes (7,37,44). Therefore, we and others (3,4,8,9,11,12,14,21,22,30,32,40,41) have begun to study the specific kinds of mutations induced by carcinogens in mammalian cells.…”

mentioning

confidence: 99%

“…But the development of shuttle vectors, i.e., plasmids carrying a defined target gene and capable of replicating in mammalian cells and also in bacteria, provides a solution to this problem (8,9,21,32,33). We are using the shuttle vector pZ189, containing the supF gene which codes for a tyrosine suppressor tRNA, to investigate at the DNA sequence level the kinds of mutations induced when DNA containing covalently bound carcinogen residues replicates in human cells.…”

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confidence: 99%

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Kinds and spectrum of mutations induced by 1-nitrosopyrene adducts during plasmid replication in human cells.

1988

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1-Nitropyrene has been shown in bacterial assays to be the principal mutagenic agent in diesel emission particulates. It has also been shown to be mutagenic in human fibroblasts and carcinogenic in animals. To investigate the kinds of mutations induced by this carcinogen and compare them with those induced by a structurally related carcinogen, (±)-7B,8a-dihydroxy-9a,10a-epoxy-7,8,9,10-tetra-hydrobenzo[a]pyrene (BPDE) (J.-L. Yang, V. M. Maher, and J. J. McCormick, Proc. Natl. Acad. Sci. USA 84:3787-3791, 1987), we treated a shuttle vector with tritiated 1-nitrosopyrene (1-NOP), a carcinogenic mutagenic intermediate metabolite of 1-nitropyrene which forms the same DNA adduct as the parent compound, and introduced the plasmids into a human embryonic kidney cell line, 293, for DNA replication to take place. The treated plasmid, pZ189, carrying a bacterial suppressor tRNA target gene, supF, was allowed 48 h to replicate in the human cells. Progeny plasmids were then rescued, purified, and introduced into bacteria carrying an amber mutation in the j-galactosidase gene in order to detect those carrying mutations in the supF gene. The frequency of mutants increased in direct proportion to the number of DNA-1-NOP adducts formed per plasmid. At the highest level of adduct formation tested, the frequency of supF mutants was 26 times higher than the background frequency of 1.4 x 10-4. DNA sequencing of 60 unequivocally independent mutants derived from

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Section: Discussionmentioning

confidence: 95%

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confidence: 99%

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confidence: 99%

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Kinds and spectrum of mutations induced by 1-nitrosopyrene adducts during plasmid replication in human cells.

1988

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“…No mutations were found during initial screening VOL. 7,1987 on May 10, 2018 by guest http://mcb.asm.org/ Downloaded from for 16 of 18 clones examined. Clone 1.11 was chosen for further study.…”

Section: Methodsmentioning

confidence: 99%

Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system.

DuBridge¹,

Tang²,

Hsia³

et al. 1987

Mol. Cell. Biol.

1,011

640

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We developed highly sensitive shuttle vector systems for detection of mutations formed in human cells using autonomously replicating derivatives of Epstein-Barr virus (EBV). EBV vectors carrying the bacterial lacI gene as the target for mutation were established in human cells and later returned to Escherichia coli for rapid detection and analysis of lacl mutations. The majority of the clonal cell lines created by establishment of the lacl-EBV vector show spontaneous LacI frequencies of less than 10-5 and are suitable for studies of induced mutation. The ability to isolate clonal lines represents a major advantage of the EBV vectors over transiently replicating shuttle vectors (such as those derived from simian virus 40) for the study of mutation. The DNA sequence changes were determined for 61 lacI mutations induced by exposure of one of the cell lines to N-nitroso-N-methylurea. A total of 33 of 34 lacI nonsense mutations and 26 of 27 missense mutations involve G C to A. T transitions. These data provide support for the mutational theory of cancer.

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“…135 EBV-based episomal vectors bear the additional advantage that they replicate only once per cell cycle, in S phase, along with chromosomal DNA. 136,137 The importance of controlled replication is that it ensures low rates of spontaneous mutation (less than 1/10 5 ) and recombination events, 119,138 although rearrangements of these vectors have rarely been described. 139 Combination of EBV-based episomal vectors with mammalian origins of replication has given them a broader host cell permissiveness.…”

Section: 78mentioning

confidence: 99%

Genetic modification of hematopoietic stem cells with nonviral systems: past progress and future prospects

2005

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Chemically induced mutagenesis in a shuttle vector with a low-background mutant frequency.

Cited by 76 publications

References 23 publications

Kinds and spectrum of mutations induced by 1-nitrosopyrene adducts during plasmid replication in human cells.

Kinds and spectrum of mutations induced by 1-nitrosopyrene adducts during plasmid replication in human cells.

Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system.

Genetic modification of hematopoietic stem cells with nonviral systems: past progress and future prospects

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