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Article
Open AccessMap** mitochondrial heteroplasmy in a Leydig tumor by laser capture micro-dissection and cycling temperature capillary electrophoresis
The growth of tumor cells is accompanied by mutations in nuclear and mitochondrial genomes creating marked genetic heterogeneity. Tumors also contain non-tumor cells of various origins. An observed somatic mit...
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Article
Open AccessThe study of calcified atherosclerotic arteries: an alternative to evaluate the composition of a problematic tissue reveals new insight including metakaryotic cells
Calcifications of atherosclerotic plaques represent a controversial issue as they either lead to the stabilization or rupture of the lesion. However, the cellular key players involved in the progression of the...
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Article
Analysis of mutational spectra by denaturing capillary electrophoresis
The point mutational spectrum over nearly any 75- to 250-bp DNA sequence isolated from cells, tissues or large populations may be discovered using denaturing capillary electrophoresis (DCE). A modification of ...
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Article
Open AccessTechnology to accelerate pangenomic scanning for unknown point mutations in exonic sequences: cycling temperature capillary electrophoresis (CTCE)
Rapid means to discover and enumerate unknown mutations in the exons of human genes on a pangenomic scale are needed to discover the genes carrying inherited risk for common diseases or the genes in which soma...
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Article
Stem cell stages and the origins of colon cancer
Analysis of historical age-specific colorectal cancer rates, present day age-specific colonic adenoma prevalence and the few reports of direct measurements of genetic change in human tissues as a function of a...
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Article
Multistage carcinogenesis and the fraction at risk
Multistage carcinogenesis models describe the evolution of the cells in an individual’s organ from a normal stage to a pre-neoplastic stage to a neoplastic stage. The triggers for the passage from one stage to...
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Article
Have environmental mutagens caused oncomutations in people?
Age-specific cancer rates show large historical increases that indict environmental risk factors. But these environmental factors did not necessarily act by increasing oncomutation rates. Mathematical analyses...
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Protocol
Scanning Low-Frequency Point Mutants in the Mitochondrial Genome Using Constant Denaturant Capillary Electrophoresis
The ability to measure rare mutational events in mitochondrial genomes from human blood and tissues without resorting to phenotypic selection is invaluable. It is essential for the study of the cause(s) of mitoch...
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Article
High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection
Researchers in several laboratories have reported a high frequency of homoplasmic mitochondrial DNA (mtDNA) mutations in human tumors1,2,3,4,5,6. This observation has been interpreted to reflect a replicative adv...
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Chapter and Conference Paper
A Stochastic Model of Carcinogenesis
This paper derives the age-dependent risk of a theoretical model of carcinogenesis incorporating the familiar notions of multiple stages (initiation, promotion and progression). It is assumed that initiation i...
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Protocol
Applications of Constant Denaturant Capillary Electrophoresis and Complementary Procedures
Constant denaturant capillary electrophoresis (CDCE) separates macromolecules based on differences in their melting temperatures. The specific apparatus and operating conditions have been described previously ...
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Protocol
High Resolution Analysis of Point Mutations by Constant Denaturant Capillary Electrophoresis (CDCE)
In recent years, the need for techniques capable of detecting and identifying point mutants has increased dramatically in the fields of genomics, cancer research, and molecular diagnostics. The large arsenal o...
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Article
Screening for human mitochondrial DNA polymorphisms with denaturing gradient gel electrophoresis
A method involving denaturing gradient gel electrophoresis (DGGE) was developed to detect mitochondrial DNA (mtDNA) polymorphisms in human peripheral T-lymphocytes. DGGE analysis of 100- to 200-bp sequences of...
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Article
Multi-copy nuclear pseudogenes of mitochondrial DNA reveal recent acute genetic changes in the human genome
Four nuclear pseudogenes homologous to the 10031–10195-bp region of the human mitochondrial genome were detected by constant denaturant capillary electrophoresis. Among them, one pseudogene is present as at le...
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Chapter
Measurement of Mutation Spectra as a Molecular Dosimeter
Most presentations in this meeting take as an article of faith that knowledge of the amount and kinds of human chemical exposure are of value in determining the causes of human cancer. It can be argued however...
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Chapter
Use of Gradient Denaturing Gels to Determine Mutational Spectrum in Human Cells
Based on the fact that mutagens induce specific patterns of gene mutations, this paper outlines a method to allow discrimination among mutagen-treated populations. The technique should allow direct screening o...
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Chapter
Mutation in Single-Cell Systems Induced by Low-Level Mutagen Exposure
A principal question currently facing toxicologists and radio-biologists concerns how measurements can be made of mutations induced by low levels of chemicals or radiation. In this paper, we focus on measureme...
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Chapter
Discrimination between Spontaneous and Induced Mutations in Human Cell Populations by use of Mutational Spectra
The central premise of genetic toxicology is that environmental agents are responsible for genetic changes in man. This premise has not been tested and we thus have not confirmed if mutations in the population...
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Chapter
Soot Components as Genetic Hazards
The study of combustion effluents potential health effects involves identifying the substances present and estimating the probable health hazards of each. Unfortunately, there are no methods which permit such ...
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Chapter
Analysis of Chemically Induced Mutation in Single Cell Populations
This discussion is about tools to analyze the complex relationship between chemicals and mutation in a relatively simple biological system: the exponentially growing single cell population. Three assumptions a...
