Substrate‐specificity of <i>uvr</i> excision repair

Murray, Michael L.

doi:10.1002/em.2860010406

Cited by 21 publications

(10 citation statements)

References 41 publications

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“…Despite the inherent limitations of extrapolating reversion data to target sequences, since multiple pathways of reversion to a His+ phenotype exist, it is still instructive to consider likely sequences affected by the anthracyclines. al, 1979;Quigley et al, 19801 alone cannot account for the apparent strain preference since, in each of the mutants examined, the mutational sequence is GC rich [Maron and Ames, 19831. Of especial interest are the near identities of the sequences CCC and CCCC at the primary sites of the -1 [Isono and Yourno, 19741, and + 1 [Ames et al, 19751 frameshift mutations, respectively.…”

Section: Discussionmentioning

confidence: 99%

Genetic and physiological modulation of anthracycline‐induced mutagenesis in Salmonella typhimurium

Cebula

1986

Environ. mutagen

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The genotoxic properties of adriamycin and daunomycin, anthracycline antibiotics effective in the treatment of a wide variety of malignancies, were examined in the Salmonella/Ames reverse-mutation test. A novel time- and temperature-dependent phenomenon that potentiates the mutagenicity of these compounds, termed mutational enhancement, is described. The results of congeneric and chemical attenuation studies imply that anthracycline-induced free radicals contribute substantively to the mutagenic potentials of adriamycin and daunomycin. These studies show that adriamycin and daunomycin are not simple intercalative compounds. Rather, anthracycline-induced mutagenesis entails at least two separate but intimately related steps, namely, intercalation within discrete base sequences and the free-radical-mediated events that ensue. Implications of the nonrandom and site-specific action of the anthracyclines are discussed.

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Section: Discussionmentioning

confidence: 99%

Genetic and physiological modulation of anthracycline‐induced mutagenesis in Salmonella typhimurium

Cebula

1986

Environ. mutagen

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“…For instance, uvr-strains cannot recognize DNA helix distortions; agents differentially lethal to uvr-strains but not mutagenic are most likely to be strand crosslinkers (Murray, 1979). Green and Muriel (1976) give five classes of damaging agents and note that some mutagens fit in more than one category.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Bioassays in the Analysis of Complex Environmental Mixtures II

1980

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“…Excision repair mechanisms are important in the repair of alkylated DNA (41). A deˆciency in excision repair genes increased the mutagenicity of the nitrosamines, and the action of AGT was aŠected by the presence of excision repair.…”

Section: Mutagenic Proˆles Of Chlorinated Nitrosaminesmentioning

confidence: 99%

Cross-linkable Nitrosamines with a Chloroalkyl Group as Candidates for Anticancer Lead Compounds

Ishikawa

Mochizuki

2007

Genes and Environment

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DNA alkylation and cross-linking are classical mechanisms underlying the activity of cancer chemotherapeutic agents such as procarbazine and mitomycin C, which are currently used in the clinic. Chloroethyl N-nitrosoureas is one group of anticancer cross-linking agents, and exert their biological activities by formation of DNA cross-links. Because anticancer chloroethyl N-nitrosoureas shows toxic side-eŠects due to protein carbamoylation, many eŠorts have been exercised to reduce unwanted sideeŠects by design of new drugs with low carbamoylating activity. N-Nitrosamines, another category of N-nitroso compounds, alkylate cellular nucleophiles in vivo, and might induce gene mutation and lead to carcinogenesis by DNA alkylation. Its active form is released after elimination of aldehyde; i.e. N-nitrosamines do not carbamoylate proteins. We have an interest in structure modiˆcation of alkylating nitrosamines as useful candidates for anticancer lead compounds. Three N-nitroso-N-(acetoxymethyl)-vchloroalkylamines, chloroethyl, chloropropyl and chlorobutylamines have been synthesized and their chemical and biological properties were evaluated. The chloropropyl nitrosamine showed mutagenicity in Salmonella typhimurium TA92 that is positively responsive to DNA cross-linker, and also showed interstrand cross-linking activity towards plasmid DNA assayed by agarose gel electrophoresis. Then three-ring aromatic moieties were introduced into the structure of chloropropyl nitrosamine to potentiate its binding a‹nity to DNA molecules. Although three aromatic analogs intercalated to double-stranded DNA, only acridine analog had DNA cross-linking activity. In TA92 strain, the acridine analog showed the highest mutagenicity among all nine N-nitroso compounds used in this study. These results suggest that the aromatic ring moiety confers DNA-intercalating ability to the cross-linkable chloropropyl nitrosamine; the acridine analog that forms DNA cross-links e‹ciently might be a potential new anticancer lead compound. To assess the application of cross-linkable nitrosamines as new anticancer agents, further investigations such as that on DNA adducts or on their activity towards cancer cells are required.

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Substrate‐specificity of uvr excision repair

Cited by 21 publications

References 41 publications

Genetic and physiological modulation of anthracycline‐induced mutagenesis in Salmonella typhimurium

Genetic and physiological modulation of anthracycline‐induced mutagenesis in Salmonella typhimurium

Short-Term Bioassays in the Analysis of Complex Environmental Mixtures II

Cross-linkable Nitrosamines with a Chloroalkyl Group as Candidates for Anticancer Lead Compounds

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