Lethal mutagenesis is a broad-spectrum antiviral strategy that employs mutagenic nucleoside analogs to exploit the high mutation rate and low mutational tolerance of many RNA viruses. Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics. We have previously demonstrated the effective lethal muta...

Four urinary metabolites of the cytostatic drug cyclophosphamide were tested for mutagenicity in the Ames Salmonella assay: nornitrogen mustard (NM), 4-ketocyclophosphamide, 3-(2-chloroethyl)oxazolidone (OZ), and N,N'-bis(2-chloroethyl)piperazine. All four acted as direct base substitution mutagens although 4-ketocyclophosphamide showed an increase in mutagenicity after metabolic activation wit...

Mutagen sensitivity in in vitro cultured lymphocytes challenged by benzo[a]pyrene diolepoxide (BPDE) has been validated as an intrinsic susceptibility factor for several cancers. Bulky BPDE-DNA adducts are repaired via either transcription-coupled repair or global genome nucleotide excision repair depending on the location of lesions. Cockayne syndrome A (CSA) and B (CSB) play essential roles i...

RNA viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in RNA virus populations. A high mutation frequency is a central tenet of the quasispecies theory. A corollary of the quasispecies theory postulates that, given their high mutation frequency, animal RNA viruses may be susceptible to error catastrophe, where they undergo a sharp dro...

Mutagen sensitivity is regarded as a genetic susceptibility phenotype for various cancers; it is cytogenetically based and probably involves a number of genes from different DNA repair pathways. This assay has been used in a number of laboratories in the field of epidemiology, where it has been investigated and appears to be a useful susceptibility biomarker for epidemiological studies assessin...

In this paper, we describe a method to enhance the fluorescence signal of mutagen detection using SOS response-induced green fluorescence protein (GFP) in genetically modified Escherichia coli using a multi-layered substrate. To generate E. coli that express SOS response-induced GFP, we constructed a plasmid carrying the RecA promoter located upstream of the GFP gene and used it to transform E...

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The investigation of the link between diet and cancer in man has resulted in the identification of a variety of carcinogenic and mutagenic principles in food, particularly cooked meat (Furihata & Matsushima, 1986), the most mutagenic of these compounds being the amino-imidazoaza-arenes:2amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx...